General Information:

Id: 7,173
Diseases: Cancer
Ciliopathy
Nephronophthisis
Mammalia
review
Reference: [PMID: 26045258]

Interaction Information:

Comment Salient properties of the Hippo pathway are in regulating cell proliferation, survival, and differentiation – all of which are particularly important processes in tissue development and regeneration. Deregulation of this pathway is furthermore implicated in cancer development.
Formal Description
Interaction-ID: 70418

process

hippo signaling

affects_activity of

Comment Salient properties of the Hippo pathway are in regulating cell proliferation, survival, and differentiation – all of which are particularly important processes in tissue development and regeneration. Deregulation of this pathway is furthermore implicated in cancer development.
Formal Description
Interaction-ID: 70639

process

hippo signaling

affects_activity of

Comment Salient properties of the Hippo pathway are in regulating cell proliferation, survival, and differentiation – all of which are particularly important processes in tissue development and regeneration. Deregulation of this pathway is furthermore implicated in cancer development.
Formal Description
Interaction-ID: 70640

process

hippo signaling

affects_activity of

disease

Cancer

Comment Downstream effectors of the Hippo kinase cascade are the paralogs and transcriptional coactivators YAP and TAZ (also known as WWTR1). The Hippo kinase cascade is the major regulator of YAP/TAZ by phosphorylating YAP/TAZ and thereby inhibiting their nuclear activities.
Formal Description
Interaction-ID: 70641

process

hippo signaling

decreases_activity of

gene/protein

YAP1

in nucleus
Comment Downstream effectors of the Hippo kinase cascade are the paralogs and transcriptional coactivators YAP and TAZ (also known as WWTR1). The Hippo kinase cascade is the major regulator of YAP/TAZ by phosphorylating YAP/TAZ and thereby inhibiting their nuclear activities.
Formal Description
Interaction-ID: 70642

process

hippo signaling

decreases_activity of

gene/protein

WWTR1

in nucleus
Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70643

gene/protein

LATS1

increases_phosphorylation of

gene/protein

YAP1

Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70644

gene/protein

LATS2

increases_phosphorylation of

gene/protein

YAP1

Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70645

gene/protein

LATS1

increases_phosphorylation of

gene/protein

WWTR1

Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70646

gene/protein

LATS2

increases_phosphorylation of

gene/protein

WWTR1

Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70647

gene/protein

YAP1

affects_activity of

gene/protein

TEAD1

Comment The Hippo pathway responds to various upstream stimuli from the cellular micro-environment including mechanical signals, cellular stress, extracellular stimuli, polarity, and adhesion cues that are integrated through upstream regulators. These upstream regulators promote the activation of the Hippo kinase cascade by activating the mammalian Ser/Thr kinases LATS1/2, which phosphorylate and promote either the cytoplasmic retention of YAP and TAZ via a 14-3-3 interaction or the degradation of YAP/TAZ, ultimately preventing TEAD-mediated transcription.
Formal Description
Interaction-ID: 70648

gene/protein

WWTR1

affects_activity of

gene/protein

TEAD1

Comment The mammalian Misshapen homolog MAP4K4 activates LATS2.
Formal Description
Interaction-ID: 70649

gene/protein

MAP4K4

increases_activity of

gene/protein

LATS2

Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70650

gene/protein

YAP1

is localized in

cellular component

cytosol

in dense cells
Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70651

gene/protein

WWTR1

is localized in

cellular component

cytosol

in dense cells
Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70652

gene/protein

YAP1

is localized in

cellular component

nucleus

in sparse cells
Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70653

gene/protein

WWTR1

is localized in

cellular component

nucleus

in sparse cells
Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70654

gene/protein

SCRIB

affects_activity of

gene/protein

YAP1

Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70655

gene/protein

SCRIB

affects_activity of

gene/protein

WWTR1

Comment While YAP and TAZ are found in the cytosol and the tight junctions in dense cells, these transcriptional coactivators translocate to the nucleus and activate TEAD-mediated transcription in sparse cells. This regulation is mediated primarily via homophilic cell–cell contacts that activate the kinase module. In addition, the basolateral junction proteins, including mammalian Scribble (SCRIB) facilitate the activation of the core kinases MST and LATS, thereby inhibiting the nuclear activities of YAP/TAZ in mammary epithelial cells. Loss of cell polarity via induction of the epithelial–mesenchymal transition (EMT) causes SCRIB delocalization and TAZ activation, which confers self-renewal and tumor-initiation capacities on breast cancer stem cells.
Formal Description
Interaction-ID: 70656

affects_activity of

gene/protein

SCRIB

Comment The apical membrane-associated FERM-domain protein neuro-fibromatosis 2 (NF2) and the WW and C2 domain-containing protein kidney and brain expressed protein (KIBRA) (also known as WWC1) form a complex to activate the core kinase cassette.
Formal Description
Interaction-ID: 70657

gene/protein

NF2

interacts (colocalizes) with

gene/protein

WWC1

Comment At adherens junctions in the inner cells of preimplantation embryos, NF2 directly interacts with alpha-catenin and AMOT to recruit LATS kinases, which in turn activates the kinase module of the Hippo pathway and thereby regulates lineage specification in preimplantation embryos.
Formal Description
Interaction-ID: 70658

gene/protein

NF2

interacts (colocalizes) with

gene/protein

CTNNA

at adherens junctions
Comment At adherens junctions in the inner cells of preimplantation embryos, NF2 directly interacts with alpha-catenin and AMOT to recruit LATS kinases, which in turn activates the kinase module of the Hippo pathway and thereby regulates lineage specification in preimplantation embryos.
Formal Description
Interaction-ID: 70659

gene/protein

NF2

interacts (colocalizes) with

gene/protein

AMOT

at adherens junctions
Comment NF2 interacts with numerous proteins that are localized at the plasma membrane, including alpha-catenin and Angiomotin (AMOT) at adherens junctions, but also localizes in the nucleus.
Formal Description
Interaction-ID: 70660

gene/protein

NF2

is localized in

cellular component

plasma membrane

Comment At the plasma membrane of cultured cells, NF2 was shown to recruit LATS kinases and coordinate their activating phosphorylation by the MST–SAV1 kinase complex, highlighting the plasma membrane as a critical subcellular compartment for Hippo signal transduction.
Formal Description
Interaction-ID: 70661

gene/protein

NF2

increases_activity of

gene/protein

LATS1

via the MST–SAV1 kinase complex
Comment NF2 interacts with numerous proteins that are localized at the plasma membrane, including alpha-catenin and Angiomotin (AMOT) at adherens junctions, but also localizes in the nucleus.
Formal Description
Interaction-ID: 70662

gene/protein

NF2

is localized in

cellular component

nucleus

Comment At the plasma membrane of cultured cells, NF2 was shown to recruit LATS kinases and coordinate their activating phosphorylation by the MST–SAV1 kinase complex, highlighting the plasma membrane as a critical subcellular compartment for Hippo signal transduction.
Formal Description
Interaction-ID: 70663

gene/protein

NF2

increases_activity of

gene/protein

LATS2

via the MST–SAV1 kinase complex
Comment At the plasma membrane of cultured cells, NF2 was shown to recruit LATS kinases and coordinate their activating phosphorylation by the MST–SAV1 kinase complex, highlighting the plasma membrane as a critical subcellular compartment for Hippo signal transduction.
Formal Description
Interaction-ID: 70664

complex/PPI

MST-SAV1 complex

increases_activity of

gene/protein

LATS1

via phosphorylation
Comment At the plasma membrane of cultured cells, NF2 was shown to recruit LATS kinases and coordinate their activating phosphorylation by the MST–SAV1 kinase complex, highlighting the plasma membrane as a critical subcellular compartment for Hippo signal transduction.
Formal Description
Interaction-ID: 70665

complex/PPI

MST-SAV1 complex

increases_activity of

gene/protein

LATS2

via phosphorylation
Comment NF2 inhibits the E3 ubiquitin ligase CRL4(DCAF1)-mediated ubiquitylation of LATS1/2 in the nucleus.
Formal Description
Interaction-ID: 70666

gene/protein

NF2

decreases_activity of

complex/PPI

E3 ubiquitin ligase CRL4(DCAF1)

Comment NF2 inhibits the E3 ubiquitin ligase CRL4(DCAF1)-mediated ubiquitylation of LATS1/2 in the nucleus.
Formal Description
Interaction-ID: 70667

gene/protein

NF2

decreases_ubiquitination/sumoylation of

gene/protein

LATS1

via E3 ubiquitin ligase CRL4(DCAF1)
Comment NF2 inhibits the E3 ubiquitin ligase CRL4(DCAF1)-mediated ubiquitylation of LATS1/2 in the nucleus.
Formal Description
Interaction-ID: 70668

gene/protein

NF2

decreases_ubiquitination/sumoylation of

gene/protein

LATS2

via E3 ubiquitin ligase CRL4(DCAF1)
Comment AMOT–YAP/TAZ interaction is mediated via PPxY motifs of AMOT and WW domains of YAP and TAZ and thus does not require YAP and TAZ phosphorylation by the kinase module.
Formal Description
Interaction-ID: 70669

gene/protein

AMOT

interacts (colocalizes) with

gene/protein

YAP1

Comment AMOT–YAP/TAZ interaction is mediated via PPxY motifs of AMOT and WW domains of YAP and TAZ and thus does not require YAP and TAZ phosphorylation by the kinase module.
Formal Description
Interaction-ID: 70670

gene/protein

AMOT

interacts (colocalizes) with

gene/protein

WWTR1

Comment PTPN14 utilizes its PPxY motifs to directly interact with WW domains of YAP, causing cytoplasmic localization of YAP and decreased YAP activity.
Formal Description
Interaction-ID: 70671

gene/protein

PTPN14

decreases_activity of

gene/protein

YAP1

Comment PTPN14 utilizes its PPxY motifs to directly interact with WW domains of YAP, causing cytoplasmic localization of YAP and decreased YAP activity.
Formal Description
Interaction-ID: 70672

gene/protein

PTPN14

increases_quantity of

gene/protein

YAP1

in cytoplasm
Comment The adherens junction protein alpha-catenin regulates YAP by sequestering YAP–14-3-3 protein complexes in the cytoplasm.
Formal Description
Interaction-ID: 70673

gene/protein

CTNNA

affects_activity of

gene/protein

YAP1

Comment The kinase module that mediates YAP phosphorylation is required for the interaction between alpha-catenin and YAP, as 14-3-3 binds to phosphorylated YAP only.
Formal Description
Interaction-ID: 70674

gene/protein

YWHAQ

interacts (colocalizes) with

gene/protein

YAP1

if YAP1 is phosphorylated
Comment AMOT is a filamentous actin (F-actin)-binding protein that predominantly localizes at tight junctions and F-actin competes with YAP for binding to AMOT.
Formal Description
Interaction-ID: 70675

gene/protein

AMOT

interacts (colocalizes) with

complex/PPI

F-actin

Comment LATS1/2 phosphorylate AMOT within a conserved F-actin-binding domain, which inhibits AMOT binding to F-actin thereby potentiating its inhibitory effects on YAP and TAZ activity.
Formal Description
Interaction-ID: 70676

gene/protein

LATS1

increases_phosphorylation of

gene/protein

AMOT

Comment LATS1/2 phosphorylate AMOT within a conserved F-actin-binding domain, which inhibits AMOT binding to F-actin thereby potentiating its inhibitory effects on YAP and TAZ activity.
Formal Description
Interaction-ID: 70677

gene/protein

LATS2

increases_phosphorylation of

gene/protein

AMOT

Comment LATS kinases can inhibit nuclear YAP and TAZ activity both directly and indirectly.
Formal Description
Interaction-ID: 70678

gene/protein

LATS1

decreases_activity of

gene/protein

YAP1

in nucleus
Comment LATS kinases can inhibit nuclear YAP and TAZ activity both directly and indirectly.
Formal Description
Interaction-ID: 70679

gene/protein

LATS2

decreases_activity of

gene/protein

YAP1

in nucleus
Comment LATS kinases can inhibit nuclear YAP and TAZ activity both directly and indirectly.
Formal Description
Interaction-ID: 70680

gene/protein

LATS1

decreases_activity of

gene/protein

WWTR1

in nucleus
Comment LATS kinases can inhibit nuclear YAP and TAZ activity both directly and indirectly.
Formal Description
Interaction-ID: 70681

gene/protein

LATS2

decreases_activity of

gene/protein

WWTR1

in nucleus
Comment WW domain-binding protein 2 (WBP2) interacts with YAP and TAZ in a WW domain- and PPxY motif-dependent manner, enhancing YAP and TAZ transcriptional coactivator properties.
Formal Description
Interaction-ID: 70682

gene/protein

WBP2

increases_activity of

gene/protein

YAP1

in nucleus
Comment WW domain-binding protein 2 (WBP2) interacts with YAP and TAZ in a WW domain- and PPxY motif-dependent manner, enhancing YAP and TAZ transcriptional coactivator properties.
Formal Description
Interaction-ID: 70683

gene/protein

WBP2

increases_activity of

gene/protein

WWTR1

in nucleus
Comment Multiple ankyrin repeats single KH domain-containing protein (MASK) has been shown to potentiate YAP activity through direct binding.
Formal Description
Interaction-ID: 70684

gene/protein

ANKHD1

increases_activity of

gene/protein

YAP1

Comment Nuclear YAP has been found to regulate miRNA processing.
Formal Description
Interaction-ID: 70685

gene/protein

YAP1

affects_activity of

Comment Nuclear YAP/TAZ bind and sequester DEAD box helicase 17 (DDX17) (also known as p72) to repress its association with Microprocessor, a complex that regulates miRNA processing.
Formal Description
Interaction-ID: 70686

gene/protein

YAP1

affects_activity of

gene/protein

DDX17

in nucleus
Comment Nuclear YAP/TAZ bind and sequester DEAD box helicase 17 (DDX17) (also known as p72) to repress its association with Microprocessor, a complex that regulates miRNA processing.
Formal Description
Interaction-ID: 70687

gene/protein

WWTR1

affects_activity of

gene/protein

DDX17

in nucleus
Comment Nuclear YAP/TAZ bind and sequester DEAD box helicase 17 (DDX17) (also known as p72) to repress its association with Microprocessor, a complex that regulates miRNA processing.
Formal Description
Interaction-ID: 70688

gene/protein

DDX17

interacts (colocalizes) with

complex/PPI

Microprocessor complex

in nucleus
Comment Nuclear YAP/TAZ bind and sequester DEAD box helicase 17 (DDX17) (also known as p72) to repress its association with Microprocessor, a complex that regulates miRNA processing.
Formal Description
Interaction-ID: 70689

complex/PPI

Microprocessor complex

increases_activity of

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70690

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-16

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70691

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-16

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70692

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-21

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70693

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-21

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70694

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-23a

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70695

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-23a

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70696

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-29

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70697

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-29

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70698

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-107

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70699

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-107

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70700

gene/protein

YAP1

affects_activity of

ncRNA/miRNA

mir-152

Comment Nuclear YAP/TAZ conversely stimulate the biogenesis of certain miRNAs, such as miR-16, -21, -23a, -29, -107, and -152, by increasing Dicer via the Let-7 family of miRNAs.
Formal Description
Interaction-ID: 70701

gene/protein

WWTR1

affects_activity of

ncRNA/miRNA

mir-152

Comment The cytoplasmic retention of YAP/TAZ via its phosphorylation results in the sequestration of beta-catenin in the cytoplasm and in some instances the recruitment of beta-TrCP to this complex, leading to the degradation of beta-catenin. In addition, cytoplasmic YAP/TAZ interact with disheveled (DVL) to inhibit Wnt target gene transcription.
Formal Description
Interaction-ID: 70702

gene/protein

YAP1

affects_activity of

Comment The cytoplasmic retention of YAP/TAZ via its phosphorylation results in the sequestration of beta-catenin in the cytoplasm and in some instances the recruitment of beta-TrCP to this complex, leading to the degradation of beta-catenin. In addition, cytoplasmic YAP/TAZ interact with disheveled (DVL) to inhibit Wnt target gene transcription.
Formal Description
Interaction-ID: 70703

gene/protein

WWTR1

affects_activity of

Comment The cytoplasmic retention of YAP/TAZ via its phosphorylation results in the sequestration of beta-catenin in the cytoplasm and in some instances the recruitment of beta-TrCP to this complex, leading to the degradation of beta-catenin. In addition, cytoplasmic YAP/TAZ interact with disheveled (DVL) to inhibit Wnt target gene transcription.
Formal Description
Interaction-ID: 70704

gene/protein

YAP1

interacts (colocalizes) with

gene/protein

DVL

Comment The cytoplasmic retention of YAP/TAZ via its phosphorylation results in the sequestration of beta-catenin in the cytoplasm and in some instances the recruitment of beta-TrCP to this complex, leading to the degradation of beta-catenin. In addition, cytoplasmic YAP/TAZ interact with disheveled (DVL) to inhibit Wnt target gene transcription.
Formal Description
Interaction-ID: 70705

gene/protein

WWTR1

interacts (colocalizes) with

gene/protein

DVL

Comment The tyrosine phosphatase SHP2 (encoded by the PTPN11 gene), like YAP and TAZ, shuttles between the nucleus and the cytoplasm where its nuclear localization promotes beta-catenin-dependent transcription. SHP2 is excluded from the nucleus in high-density cells by its interaction with phosphorylated YAP and TAZ.
Formal Description
Interaction-ID: 70706

gene/protein

PTPN11

increases_activity of

in nucleus
Drugbank entries Show/Hide entries for PTPN11
Comment The tyrosine phosphatase SHP2 (encoded by the PTPN11 gene), like YAP and TAZ, shuttles between the nucleus and the cytoplasm where its nuclear localization promotes beta-catenin-dependent transcription. SHP2 is excluded from the nucleus in high-density cells by its interaction with phosphorylated YAP and TAZ.
Formal Description
Interaction-ID: 70707

gene/protein

YAP1

decreases_quantity of

gene/protein

PTPN11

in nucleus; if YAP1 is phosphorylated
Drugbank entries Show/Hide entries for PTPN11
Comment The tyrosine phosphatase SHP2 (encoded by the PTPN11 gene), like YAP and TAZ, shuttles between the nucleus and the cytoplasm where its nuclear localization promotes beta-catenin-dependent transcription. SHP2 is excluded from the nucleus in high-density cells by its interaction with phosphorylated YAP and TAZ.
Formal Description
Interaction-ID: 70708

gene/protein

WWTR1

decreases_quantity of

gene/protein

PTPN11

in nucleus; if WWTR1 is phosphorylated
Drugbank entries Show/Hide entries for PTPN11
Comment Nuclear YAP/TAZ promotes nuclear beta-catenin, which mediates T cell factor (TCF)-dependent transcription.
Formal Description
Interaction-ID: 70709

gene/protein

YAP1

increases_activity of

gene/protein

CTNNB1

in nucleus
Drugbank entries Show/Hide entries for CTNNB1
Comment Nuclear YAP/TAZ promotes nuclear beta-catenin, which mediates T cell factor (TCF)-dependent transcription.
Formal Description
Interaction-ID: 70710

gene/protein

WWTR1

increases_activity of

gene/protein

CTNNB1

in nucleus
Drugbank entries Show/Hide entries for CTNNB1
Comment Nuclear YAP/TAZ facilitate nuclear translocation of SHP2, which in turn dephosphorylates CDC73 (also known as parafibromin) to stimulate CDC73–beta-catenin binding and ultimately activate Wnt target gene transcription.
Formal Description
Interaction-ID: 70711

gene/protein

PTPN11

decreases_phosphorylation of

gene/protein

CDC73

Drugbank entries Show/Hide entries for PTPN11
Comment Nuclear YAP/TAZ facilitate nuclear translocation of SHP2, which in turn dephosphorylates CDC73 (also known as parafibromin) to stimulate CDC73–beta-catenin binding and ultimately activate Wnt target gene transcription.
Formal Description
Interaction-ID: 70712

gene/protein

PTPN11

increases_quantity of

complex/PPI

CDC73-CTNNB1 complex

in nucleus
Drugbank entries Show/Hide entries for PTPN11
Comment Protein kinase C zeta (PKC-zeta) was identified to phosphorylate and thereby inhibit both beta-catenin and YAP, highlighting the atypical PKCs as mediators of intestinal homeostasis and regeneration by modulating both YAP and beta-catenin activity.
Formal Description
Interaction-ID: 70713

gene/protein

PRKCZ

decreases_activity of

gene/protein

CTNNB1

via phosphorylation
Drugbank entries Show/Hide entries for CTNNB1
Comment Protein kinase C zeta (PKC-zeta) was identified to phosphorylate and thereby inhibit both beta-catenin and YAP, highlighting the atypical PKCs as mediators of intestinal homeostasis and regeneration by modulating both YAP and beta-catenin activity.
Formal Description
Interaction-ID: 70714

gene/protein

PRKCZ

decreases_activity of

gene/protein

YAP1

via phosphorylation
Comment Active Wnt signaling increases YAP abundance and hence transcriptional activity, suggesting that Wnt target genes can also feed back on the Hippo pathway and potentiate its signaling.
Formal Description
Interaction-ID: 70715

increases_expression of

gene/protein

YAP1

Comment It remains to be determined whether YAP/TAZ-mediated, TGFbeta-dependent transcription is regulated exclusively via SMADs or whether it may also require TEADs or context-dependent partnering with diverse transcription factors.
Formal Description
Interaction-ID: 70716

affects_activity of

gene/protein

YAP1

Comment It remains to be determined whether YAP/TAZ-mediated, TGFbeta-dependent transcription is regulated exclusively via SMADs or whether it may also require TEADs or context-dependent partnering with diverse transcription factors.
Formal Description
Interaction-ID: 70717

affects_activity of

gene/protein

WWTR1

Comment TAZ induces BMP4 transcription and promotes cell migration revealing a TAZ/TEAD/ BMP signaling axis in mammary epithelial cells.
Formal Description
Interaction-ID: 70718

gene/protein

WWTR1

increases_expression of

gene/protein

BMP4

Comment Integrin-linked kinase, an integrin-associated actin and tubulin cytoskeleton-interacting effector that mediates TGFbeta signaling, was found to be a negative regulator of the Hippo kinase cascade in cancer cells by inhibiting MYPT1, which leads to inhibition of NF2 and nuclear accumulation of YAP/TAZ.
Formal Description
Interaction-ID: 70719

gene/protein

ILK

increases_activity of

Comment Integrin-linked kinase, an integrin-associated actin and tubulin cytoskeleton-interacting effector that mediates TGFbeta signaling, was found to be a negative regulator of the Hippo kinase cascade in cancer cells by inhibiting MYPT1, which leads to inhibition of NF2 and nuclear accumulation of YAP/TAZ.
Formal Description
Interaction-ID: 70720

gene/protein

ILK

decreases_activity of

process

hippo signaling

in cancer cells
Comment Integrin-linked kinase, an integrin-associated actin and tubulin cytoskeleton-interacting effector that mediates TGFbeta signaling, was found to be a negative regulator of the Hippo kinase cascade in cancer cells by inhibiting MYPT1, which leads to inhibition of NF2 and nuclear accumulation of YAP/TAZ.
Formal Description
Interaction-ID: 70721

gene/protein

ILK

decreases_activity of

gene/protein

PPP1R12A

in cancer cells
Comment Integrin-linked kinase, an integrin-associated actin and tubulin cytoskeleton-interacting effector that mediates TGFbeta signaling, was found to be a negative regulator of the Hippo kinase cascade in cancer cells by inhibiting MYPT1, which leads to inhibition of NF2 and nuclear accumulation of YAP/TAZ.
Formal Description
Interaction-ID: 70722

gene/protein

ILK

decreases_activity of

gene/protein

NF2

in cancer cells
Comment A prominent role for GPCRs and their cognate ligands as regulators of Hippo signaling has been established. GPCRs are coupled to small heterotrimeric G proteins and YAP/TAZ nuclear activities are either activated or inhibited depending on the G proteins coupled to the active receptors.
Formal Description
Interaction-ID: 70723
Comment A prominent role for GPCRs and their cognate ligands as regulators of Hippo signaling has been established. GPCRs are coupled to small heterotrimeric G proteins and YAP/TAZ nuclear activities are either activated or inhibited depending on the G proteins coupled to the active receptors.
Formal Description
Interaction-ID: 70724

affects_activity of

gene/protein

YAP1

Comment A prominent role for GPCRs and their cognate ligands as regulators of Hippo signaling has been established. GPCRs are coupled to small heterotrimeric G proteins and YAP/TAZ nuclear activities are either activated or inhibited depending on the G proteins coupled to the active receptors.
Formal Description
Interaction-ID: 70725

affects_activity of

gene/protein

WWTR1

Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70726

drug/chemical compound

Lysophosphatidic acid

affects_activity of

Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70727

drug/chemical compound

Sphingosine 1-phosphate

affects_activity of

Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70728

drug/chemical compound

Lysophosphatidic acid

increases_activity of

gene/protein

YAP1

in nucleus
Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70729

drug/chemical compound

Lysophosphatidic acid

increases_activity of

gene/protein

WWTR1

in nucleus
Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70730

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

gene/protein

YAP1

in nucleus
Comment The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) work through GPCRs via G(alpha)12/13 and are potent inhibitors of the Hippo kinase module and thereby activators of nuclear YAP/TAZ.
Formal Description
Interaction-ID: 70731

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

gene/protein

WWTR1

in nucleus
Comment Ligands such as epinephrine work via G(alpha)S-coupled GPCRs to inhibit YAP/TAZ through PKA-mediated activation of LATS kinases.
Formal Description
Interaction-ID: 70732

drug/chemical compound

Adrenaline

decreases_activity of

gene/protein

YAP1

in nucleus
Comment Ligands such as epinephrine work via G(alpha)S-coupled GPCRs to inhibit YAP/TAZ through PKA-mediated activation of LATS kinases.
Formal Description
Interaction-ID: 70733

drug/chemical compound

Adrenaline

decreases_activity of

gene/protein

WWTR1

in nucleus
Comment YAP and TAZ are activated by the EGF family of ligands.
Formal Description
Interaction-ID: 70734

increases_activity of

gene/protein

YAP1

Comment YAP and TAZ are activated by the EGF family of ligands.
Formal Description
Interaction-ID: 70735

increases_activity of

gene/protein

WWTR1

Comment EGF inhibits the kinase module via 3-phosphoinositide dependent protein kinase 1 (PDPK1) and AJUBA proteins, which leads to impairment of SAV1’s role in the kinase complex.
Formal Description
Interaction-ID: 70736

affects_activity of

gene/protein

PDPK1

Drugbank entries Show/Hide entries for PDPK1
Comment EGF inhibits the kinase module via 3-phosphoinositide dependent protein kinase 1 (PDPK1) and AJUBA proteins, which leads to impairment of SAV1’s role in the kinase complex.
Formal Description
Interaction-ID: 70737

affects_activity of

gene/protein

AJUBA

Comment EGF inhibits the kinase module via 3-phosphoinositide dependent protein kinase 1 (PDPK1) and AJUBA proteins, which leads to impairment of SAV1’s role in the kinase complex.
Formal Description
Interaction-ID: 70738

affects_activity of

gene/protein

SAV1

Comment Activation of YAP/TAZ results in the transcription of the EGF-like growth factor AREG, providing crosstalk between Hippo and EGF signaling.
Formal Description
Interaction-ID: 70739

gene/protein

YAP1

increases_expression of

gene/protein

AREG

Comment Activation of YAP/TAZ results in the transcription of the EGF-like growth factor AREG, providing crosstalk between Hippo and EGF signaling.
Formal Description
Interaction-ID: 70740

gene/protein

WWTR1

increases_expression of

gene/protein

AREG

Comment Activation of YAP/TAZ results in the transcription of the EGF-like growth factor AREG, providing crosstalk between Hippo and EGF signaling.
Formal Description
Interaction-ID: 70741

gene/protein

AREG

affects_activity of

Comment A direct link between Notch signaling and YAP has become apparent in several systems, such as the developing embryo, neuronal stem cells, mature hepatocytes, and hepatocyte-derived stem cells. The ligand Jagged1 (JAG1) and the receptor NOTCH2, both known to be critical determinants of biliary cell fate, are direct YAP–TEAD target genes. Inducing YAP activity in vivo can reprogram hepatocytes via NOTCH activation into progenitor cells.
Formal Description
Interaction-ID: 70742

gene/protein

YAP1

affects_activity of

Comment Hippo and NOTCH signaling play an important role during mouse embryogenesis from the morula to the blastocyst stage when the trophectoderm (TE), which gives rise to the placenta, and the inner cell mass (ICM), which gives rise to the embryo proper, lineages are specified.
Formal Description
Interaction-ID: 70743

process

hippo signaling

affects_activity of

Comment Hippo and NOTCH signaling play an important role during mouse embryogenesis from the morula to the blastocyst stage when the trophectoderm (TE), which gives rise to the placenta, and the inner cell mass (ICM), which gives rise to the embryo proper, lineages are specified.
Formal Description
Interaction-ID: 70744

affects_activity of

Comment The Hippo pathway both controls and is regulated by the primary cilia, a microtubule-based solitary sensory signaling organelle comprising a special part of the plasma membrane in most eukaryotic quiescent cells.
Formal Description
Interaction-ID: 70745

process

hippo signaling

affects_activity of

cellular component

cilium

Comment The Hippo pathway both controls and is regulated by the primary cilia, a microtubule-based solitary sensory signaling organelle comprising a special part of the plasma membrane in most eukaryotic quiescent cells.
Formal Description
Interaction-ID: 70746

cellular component

cilium

affects_activity of

process

hippo signaling

Comment The primary cilia respond to mechanical signals and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFbeta family, receptor tyrosine kinases, and Wnt receptors.
Formal Description
Interaction-ID: 70747

complex/PPI

G-protein coupled receptor

is localized in

cellular component

cilium

Comment The primary cilia respond to mechanical signals and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFbeta family, receptor tyrosine kinases, and Wnt receptors.
Formal Description
Interaction-ID: 70748

complex/PPI

Sonic hedgehog receptor

is localized in

cellular component

cilium

Comment The primary cilia respond to mechanical signals and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFbeta family, receptor tyrosine kinases, and Wnt receptors.
Formal Description
Interaction-ID: 70749

complex/PPI

TGF-beta receptor

is localized in

cellular component

cilium

Comment The primary cilia respond to mechanical signals and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFbeta family, receptor tyrosine kinases, and Wnt receptors.
Formal Description
Interaction-ID: 70750

complex/PPI

Receptor tyrosine kinase

is localized in

cellular component

cilium

Comment The primary cilia respond to mechanical signals and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFbeta family, receptor tyrosine kinases, and Wnt receptors.
Formal Description
Interaction-ID: 70751

complex/PPI

Wnt receptor

is localized in

cellular component

cilium

Comment Members of the nephrocystin (NPHP) family, established primary cilia-associated proteins, induce TAZ (and YAP) activity.
Formal Description
Interaction-ID: 70752

gene/protein

NPHP

increases_activity of

gene/protein

YAP1

Comment Members of the nephrocystin (NPHP) family, established primary cilia-associated proteins, induce TAZ (and YAP) activity.
Formal Description
Interaction-ID: 70753

gene/protein

NPHP

increases_activity of

gene/protein

WWTR1

Comment NPHP4 binds to LATS and negatively regulates LATS activity, whereas NPHP3 and NPHP9 bind directly to TAZ and potentially compete with 14-3-3 binding to relieve cytoplasmic retention.
Formal Description
Interaction-ID: 70754

gene/protein

NPHP4

decreases_activity of

gene/protein

LATS1

Comment NPHP4 binds to LATS and negatively regulates LATS activity, whereas NPHP3 and NPHP9 bind directly to TAZ and potentially compete with 14-3-3 binding to relieve cytoplasmic retention.
Formal Description
Interaction-ID: 70756

gene/protein

NPHP3

interacts (colocalizes) with

gene/protein

WWTR1

Comment NPHP4 binds to LATS and negatively regulates LATS activity, whereas NPHP3 and NPHP9 bind directly to TAZ and potentially compete with 14-3-3 binding to relieve cytoplasmic retention.
Formal Description
Interaction-ID: 70757

gene/protein

NEK8

interacts (colocalizes) with

gene/protein

WWTR1

Comment TAZ binds the primary cilia-associated protein GLIS family zinc finger 3 (Glis3), facilitating Glis3-mediated transcription.
Formal Description
Interaction-ID: 70759

gene/protein

WWTR1

interacts (colocalizes) with

gene/protein

GLIS3

Comment TAZ binds the primary cilia-associated protein GLIS family zinc finger 3 (Glis3), facilitating Glis3-mediated transcription.
Formal Description
Interaction-ID: 70761

gene/protein

GLIS3

increases_activity of

Comment SHH, the prototypical primary cilia signaling ligand, activates YAP transcription, abundance, and activity.
Formal Description
Interaction-ID: 70762

gene/protein

SHH

increases_expression of

gene/protein

YAP1

Comment SHH binds to the inhibitory transmembrane protein Patched and thereby relieves the GPCR-like molecule Smoothened from its inhibition, an effect that could be mediated via GPCR signaling.
Formal Description
Interaction-ID: 70763

gene/protein

SHH

interacts (colocalizes) with

gene/protein

PTCH1

Comment SHH binds to the inhibitory transmembrane protein Patched and thereby relieves the GPCR-like molecule Smoothened from its inhibition, an effect that could be mediated via GPCR signaling.
Formal Description
Interaction-ID: 70764

complex/PPI

SHH-PTCH1 complex

increases_activity of

gene/protein

SMO

Drugbank entries Show/Hide entries for SMO
Comment The upstream Hippo kinase module likewise integrates with the primary cilia, as MST and SAV1 inhibit the disassembly of primary cilia by MST-mediated phosphorylation of AURKA, an important regulator of the primary cilia disassembly complex, and by association with the NPHP transition-zone complex, thereby inducing an increase in steady-state primary cilial abundance.
Formal Description
Interaction-ID: 70765

complex/PPI

MST-SAV1 complex

decreases_activity of

Comment The upstream Hippo kinase module likewise integrates with the primary cilia, as MST and SAV1 inhibit the disassembly of primary cilia by MST-mediated phosphorylation of AURKA, an important regulator of the primary cilia disassembly complex, and by association with the NPHP transition-zone complex, thereby inducing an increase in steady-state primary cilial abundance.
Formal Description
Interaction-ID: 70766

gene/protein

MST

increases_phosphorylation of

gene/protein

AURKA

Drugbank entries Show/Hide entries for MST or AURKA
Comment The upstream Hippo kinase module likewise integrates with the primary cilia, as MST and SAV1 inhibit the disassembly of primary cilia by MST-mediated phosphorylation of AURKA, an important regulator of the primary cilia disassembly complex, and by association with the NPHP transition-zone complex, thereby inducing an increase in steady-state primary cilial abundance.
Formal Description
Interaction-ID: 70767

complex/PPI

MST-SAV1 complex

interacts (colocalizes) with

complex/PPI

B9 complex

Comment A range of diseases caused by dysfunctional primary cilia are termed ciliopathies and, intriguingly, TAZ knockout animals develop polycystic kidneys and express lower levels of multiple genes important for primary cilial morphogenesis; thus, these mice have malfunctioning cilia and exhibit a phenotype reminiscent of known human ciliopathies.
Formal Description
Interaction-ID: 70768

gene/protein

WWTR1

affects_activity of

phenotype

kidney cysts

Comment A range of diseases caused by dysfunctional primary cilia are termed ciliopathies and, intriguingly, TAZ knockout animals develop polycystic kidneys and express lower levels of multiple genes important for primary cilial morphogenesis; thus, these mice have malfunctioning cilia and exhibit a phenotype reminiscent of known human ciliopathies. By contrast, TAZ depletion in tissue culture cells such as RPE1 cells induce ciliogenesis.
Formal Description
Interaction-ID: 70769

gene/protein

WWTR1

affects_activity of

process

cilium assembly

Comment CDK1 directly phosphorylates and inhibits YAP function to induce apoptosis. However, the role of CDK1-mediated YAP phosphorylation is controversial as mitotic phosphorylation of YAP by CDK1 promotes mitotic defects and potentiates oncogenic functions of YAP.
Formal Description
Interaction-ID: 70770

gene/protein

CDK1

increases_phosphorylation of

gene/protein

YAP1

Drugbank entries Show/Hide entries for CDK1
Comment DNA damage activates the tyrosine kinase ABL through ATM–JNK signaling, which in turn phosphorylates YAP to stimulate proapoptotic functions of YAP in complex with p73.
Formal Description
Interaction-ID: 70771

increases_activity of

gene/protein

ABL1

Drugbank entries Show/Hide entries for ABL1
Comment DNA damage activates the tyrosine kinase ABL through ATM–JNK signaling, which in turn phosphorylates YAP to stimulate proapoptotic functions of YAP in complex with p73.
Formal Description
Interaction-ID: 70772

gene/protein

ABL1

increases_phosphorylation of

gene/protein

YAP1

Drugbank entries Show/Hide entries for ABL1
Comment Endoplasmic reticulum (ER) stress has been implicated in YAP regulation. The ER stress transducer PKR-like ER kinase (PERK) phosphorylates eukaryotic initiation factor 2a (eIF2a) during the adaptive stage of the unfolded protein response (UPR), which suppresses general protein synthesis and specifically induces the translation of ATF4, which regulates YAP transcription. ER stress thus induces YAP expression through the PERK–eIF2a–ATF4 axis to prevent cell death during the adaptive stage of the UPR, while prolonged ER stress activates Hippo signaling to inhibit YAP and promote apoptosis.
Formal Description
Interaction-ID: 70773

increases_expression of

gene/protein

YAP1

via the PERK–eIF2a–ATF4 axis
Comment Endoplasmic reticulum (ER) stress has been implicated in YAP regulation. The ER stress transducer PKR-like ER kinase (PERK) phosphorylates eukaryotic initiation factor 2a (eIF2a) during the adaptive stage of the unfolded protein response (UPR), which suppresses general protein synthesis and specifically induces the translation of ATF4, which regulates YAP transcription. ER stress thus induces YAP expression through the PERK–eIF2a–ATF4 axis to prevent cell death during the adaptive stage of the UPR, while prolonged ER stress activates Hippo signaling to inhibit YAP and promote apoptosis.
Formal Description
Interaction-ID: 70774

gene/protein

EIF2AK3

increases_phosphorylation of

gene/protein

EIF2A

Comment Endoplasmic reticulum (ER) stress has been implicated in YAP regulation. The ER stress transducer PKR-like ER kinase (PERK) phosphorylates eukaryotic initiation factor 2a (eIF2a) during the adaptive stage of the unfolded protein response (UPR), which suppresses general protein synthesis and specifically induces the translation of ATF4, which regulates YAP transcription. ER stress thus induces YAP expression through the PERK–eIF2a–ATF4 axis to prevent cell death during the adaptive stage of the UPR, while prolonged ER stress activates Hippo signaling to inhibit YAP and promote apoptosis.
Formal Description
Interaction-ID: 70775

gene/protein

EIF2A

increases_expression of

gene/protein

ATF4

Comment Endoplasmic reticulum (ER) stress has been implicated in YAP regulation. The ER stress transducer PKR-like ER kinase (PERK) phosphorylates eukaryotic initiation factor 2a (eIF2a) during the adaptive stage of the unfolded protein response (UPR), which suppresses general protein synthesis and specifically induces the translation of ATF4, which regulates YAP transcription. ER stress thus induces YAP expression through the PERK–eIF2a–ATF4 axis to prevent cell death during the adaptive stage of the UPR, while prolonged ER stress activates Hippo signaling to inhibit YAP and promote apoptosis.
Formal Description
Interaction-ID: 70776

gene/protein

ATF4

affects_expression of

gene/protein

YAP1

Comment Endoplasmic reticulum (ER) stress has been implicated in YAP regulation. The ER stress transducer PKR-like ER kinase (PERK) phosphorylates eukaryotic initiation factor 2a (eIF2a) during the adaptive stage of the unfolded protein response (UPR), which suppresses general protein synthesis and specifically induces the translation of ATF4, which regulates YAP transcription. ER stress thus induces YAP expression through the PERK–eIF2a–ATF4 axis to prevent cell death during the adaptive stage of the UPR, while prolonged ER stress activates Hippo signaling to inhibit YAP and promote apoptosis.
Formal Description
Interaction-ID: 70777

increases_activity of

process

hippo signaling

if ER stress is prolonged
Comment Hyperosmotic stress induces tyrosine phosphorylation of TAZ by the ABL kinase, which facilitates the interaction between TAZ and nuclear factor of activated T cells 5 (NFAT5) to inhibit NFAT5 function in osmoregulatory transcription.
Formal Description
Interaction-ID: 70778

increases_phosphorylation of

gene/protein

WWTR1

via ABL kinase
Comment Hyperosmotic stress induces tyrosine phosphorylation of TAZ by the ABL kinase, which facilitates the interaction between TAZ and nuclear factor of activated T cells 5 (NFAT5) to inhibit NFAT5 function in osmoregulatory transcription.
Formal Description
Interaction-ID: 70779

increases_quantity of

complex/PPI

NFAT5-WWTR1 complex

Comment Hyperosmotic stress induces tyrosine phosphorylation of TAZ by the ABL kinase, which facilitates the interaction between TAZ and nuclear factor of activated T cells 5 (NFAT5) to inhibit NFAT5 function in osmoregulatory transcription.
Formal Description
Interaction-ID: 70780

gene/protein

WWTR1

decreases_activity of

gene/protein

NFAT5

Comment Hyperosmotic stress induces tyrosine phosphorylation of TAZ by the ABL kinase, which facilitates the interaction between TAZ and nuclear factor of activated T cells 5 (NFAT5) to inhibit NFAT5 function in osmoregulatory transcription.
Formal Description
Interaction-ID: 70781

gene/protein

NFAT5

affects_activity of

in response to hyperosmotic stress
Comment Oxidative stress evoked by ischemia and reperfusion in the mouse heart activates the Hippo pathway to antagonize a functional YAP–FOXO1 complex, leading to enhanced oxidative stress-induced cell death.
Formal Description
Interaction-ID: 70782

increases_activity of

process

hippo signaling

Comment Oxidative stress evoked by ischemia and reperfusion in the mouse heart activates the Hippo pathway to antagonize a functional YAP–FOXO1 complex, leading to enhanced oxidative stress-induced cell death.
Formal Description
Interaction-ID: 70783

process

hippo signaling

decreases_activity of

complex/PPI

FOXO1-YAP1 complex

Comment Hypoxia deactivates the Hippo pathway by destabilizing LATS2 through SIAH2 ubiquitin ligase-induced degradation.
Formal Description
Interaction-ID: 70784

decreases_activity of

process

hippo signaling

Comment Hypoxia deactivates the Hippo pathway by destabilizing LATS2 through SIAH2 ubiquitin ligase-induced degradation.
Formal Description
Interaction-ID: 70785

decreases_activity of

gene/protein

LATS2

Comment Energy stress, such as inhibition of glucose metabolism and ATP production, induces AMP-activated protein kinase (AMPK)-mediated phosphorylation of Angiomotin-like 1 (AMOTL1) to stabilize and increase AMOTL1, which in turn stimulates LATS. LATS also senses and is activated by glucose starvation in an AMPK-independent manner. In addition, AMPK inhibits YAP by directly phosphorylating it at least two distinct sites; therefore, energy stress inhibits YAP nuclear activity by several mechanisms.
Formal Description
Interaction-ID: 70786

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

AMOTL1

Comment Energy stress, such as inhibition of glucose metabolism and ATP production, induces AMP-activated protein kinase (AMPK)-mediated phosphorylation of Angiomotin-like 1 (AMOTL1) to stabilize and increase AMOTL1, which in turn stimulates LATS. LATS also senses and is activated by glucose starvation in an AMPK-independent manner. In addition, AMPK inhibits YAP by directly phosphorylating it at least two distinct sites; therefore, energy stress inhibits YAP nuclear activity by several mechanisms.
Formal Description
Interaction-ID: 70787

gene/protein

AMOTL1

increases_activity of

gene/protein

LATS

Comment Energy stress, such as inhibition of glucose metabolism and ATP production, induces AMP-activated protein kinase (AMPK)-mediated phosphorylation of Angiomotin-like 1 (AMOTL1) to stabilize and increase AMOTL1, which in turn stimulates LATS. LATS also senses and is activated by glucose starvation in an AMPK-independent manner. In addition, AMPK inhibits YAP by directly phosphorylating it at least two distinct sites; therefore, energy stress inhibits YAP nuclear activity by several mechanisms.
Formal Description
Interaction-ID: 70788

complex/PPI

AMPK

decreases_activity of

gene/protein

YAP1