General Information:

Id: 4,309
Diseases: Metabolic
Homo sapiens
BTO:0001581 embryonic stem cell line H1, H9
article
Reference: Zhou J et al.(2009) mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells Proc. Natl. Acad. Sci. U.S.A. 106: 7840-7845 [PMID: 19416884]

Interaction Information:

Comment mTOR stabilizes OCT-4, SOX2, and NANOG.
Formal Description
Interaction-ID: 44140

gene/protein

MTOR

increases_activity of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Drugbank entries Show/Hide entries for MTOR
Comment mTOR stabilizes OCT-4, SOX2, and NANOG.
Formal Description
Interaction-ID: 44141

gene/protein

MTOR

increases_activity of

gene/protein

SOX2

SOX2: marker for pluripotency
Drugbank entries Show/Hide entries for MTOR
Comment mTOR stabilizes OCT-4, SOX2, and NANOG.
Formal Description
Interaction-ID: 44142

gene/protein

MTOR

increases_activity of

gene/protein

NANOG

NANOG: marker for pluripotency
Drugbank entries Show/Hide entries for MTOR
Comment mTOR suppresses endoderm and mesoderm activities.
Formal Description
Interaction-ID: 44143

gene/protein

MTOR

decreases_activity of

tissue/cell line

endoderm

Drugbank entries Show/Hide entries for MTOR
Comment mTOR suppresses endoderm and mesoderm activities.
Formal Description
Interaction-ID: 44144

gene/protein

MTOR

decreases_activity of

tissue/cell line

mesoderm

Drugbank entries Show/Hide entries for MTOR
Comment mTOR is required for hESC proliferation.
Formal Description
Interaction-ID: 44145

gene/protein

MTOR

affects_activity of

tissue/cell line

embryonic stem cell

concerning the proliferation
Drugbank entries Show/Hide entries for MTOR
Comment mTOR is required for hESC proliferation.
Formal Description
Interaction-ID: 44146

gene/protein

MTOR

affects_activity of

of human embryonic stem cells (hESC)
Drugbank entries Show/Hide entries for MTOR
Comment mTOR supports long-term self-renewal of human embryonic stem cells.
Formal Description
Interaction-ID: 44147

gene/protein

MTOR

increases_activity of

of human embryonic stem cells
Drugbank entries Show/Hide entries for MTOR
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44148

gene/protein

MTOR

decreases_expression of

gene/protein

TBXT

if mTOR is activated up-regulation of T gene is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Downstream signals of mTOR: mTOR inhibition resulted in a rapid, robust, and continuous up-regulation of several differentiation-promoting transcription factors, including Mix1 homeobox-like 1 (MIXL1), T gene, early B-cell factor 2 (EBF2), and the homeobox protein PITX2.
Formal Description
Interaction-ID: 44149

gene/protein

MTOR

affects_expression of

gene/protein

MIXL1

inhibition of mTOR results in an up-regulation of MIXL1
Drugbank entries Show/Hide entries for MTOR
Comment The suppression of mTOR leaads to a modest but consistent up-regulation of EOMES, a gene required for mesoderm differentiation.
Formal Description
Interaction-ID: 44150

gene/protein

EOMES

affects_activity of

Comment Ectopic expression of EBF2 impaired the compact morphology of hESCs and markedly down-regulated the expression of SOX2, NANOG, and POU5F1.
Formal Description
Interaction-ID: 44151

gene/protein

EBF2

decreases_expression of

gene/protein

SOX2

SOX2: marker for pluripotency
Comment Overexpression of MIXL1 induced modest down-regulation of SOX2 and NANOG.
Formal Description
Interaction-ID: 44152

gene/protein

MIXL1

affects_expression of

gene/protein

SOX2

if MIXL1 is overexpressed the marker for pluripotency SOX2 is down-regulated
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44153

gene/protein

WNT3A

increases_expression of

gene/protein

MIXL1

in H9 cells
Comment In response to rapamycin treatment, H9 cells up-regulated gene expression of CCNG2 (which encodes Cyclin G2) and programmed cell death 4 (PDCD4), both of which inhibit cell proliferation.
Formal Description
Interaction-ID: 44154

drug/chemical compound

Rapamycin

increases_expression of

gene/protein

CCNG2

in H9 cells
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44155

gene/protein

CCNG2

affects_activity of

process

cell growth

Overexpression of Cyclin G2 markedly reduced cell growth.
Comment Hypothesis: Suppression of both Cyclin G2 and PDCD4 expression by mTOR plays a role in promoting hESC proliferation, while inhibition of the Wnt signaling pathway and the suppression of a subset of differentiation-promoting transcription factors are essential for maintaining the undifferentiated state of hESCs. Results raise the possibility that mTOR inhibits also the transcriptional activity of MIXL1, T gene, PITX2, and EBF2 independently of the OCT-4/SOX2/NANOG circuitry. Alternatively, mTOR inhibition could cause rapid perturbations of NANOG, SOX2, and OCT-4 functions (e.g., via posttranslational modifications) before reduction of their protein levels, which would subsequently lead to the differentiation activities.
Formal Description
Interaction-ID: 44156

none selected

Drugbank entries Show/Hide entries for or
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44158

gene/protein

MTOR

decreases_expression of

gene/protein

MESP1

if mTOR is activated up-regulation of MESP1 is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44162

gene/protein

MTOR

decreases_expression of

gene/protein

GATA4

if mTOR is activated up-regulation of GATA4 is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44163

gene/protein

MTOR

decreases_expression of

gene/protein

GATA6

if mTOR is activated up-regulation of GATA6 is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44166

gene/protein

MTOR

decreases_expression of

gene/protein

EOMES

if mTOR is activated up-regulation of EOMES is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Activation of mTOR effectively repressed up-regulation of T gene, MESP1, GATA4, GATA6, EOMES, and SOX17.
Formal Description
Interaction-ID: 44167

gene/protein

MTOR

decreases_expression of

gene/protein

SOX17

if mTOR is activated up-regulation of SOX17 is repressed
Drugbank entries Show/Hide entries for MTOR
Comment Downstream signals of mTOR: mTOR inhibition resulted in a rapid, robust, and continuous up-regulation of several differentiation-promoting transcription factors, including Mix1 homeobox-like 1 (MIXL1), T gene, early B-cell factor 2 (EBF2), and the homeobox protein PITX2.
Formal Description
Interaction-ID: 44168

gene/protein

MTOR

affects_expression of

gene/protein

EBF2

inhibition of mTOR results in an up-regulation of EBF2
Drugbank entries Show/Hide entries for MTOR
Comment Downstream signals of mTOR: mTOR inhibition resulted in a rapid, robust, and continuous up-regulation of several differentiation-promoting transcription factors, including Mix1 homeobox-like 1 (MIXL1), T gene, early B-cell factor 2 (EBF2), and the homeobox protein PITX2.
Formal Description
Interaction-ID: 44169

gene/protein

MTOR

affects_expression of

gene/protein

PITX2

inhibition of mTOR results in an up-regulation of PITX2
Drugbank entries Show/Hide entries for MTOR
Comment Ectopic expression of EBF2 impaired the compact morphology of hESCs and markedly down-regulated the expression of SOX2, NANOG, and POU5F1.
Formal Description
Interaction-ID: 44171

gene/protein

EBF2

decreases_expression of

gene/protein

NANOG

NANOG: marker for pluripotency
Comment Ectopic expression of EBF2 impaired the compact morphology of hESCs and markedly down-regulated the expression of SOX2, NANOG, and POU5F1.
Formal Description
Interaction-ID: 44172

gene/protein

EBF2

decreases_expression of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Comment Overexpression of MIXL1 induced modest down-regulation of SOX2 and NANOG.
Formal Description
Interaction-ID: 44174

gene/protein

MIXL1

affects_expression of

gene/protein

NANOG

if MIXL1 is overexpressed the marker for pluripotency NANOG is down-regulated
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44176

gene/protein

WNT3A

increases_expression of

gene/protein

T

in H9 cells
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44177

gene/protein

WNT3A

increases_expression of

gene/protein

PITX2

in H9 cells
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44179

gene/protein

WNT3A

increases_expression of

gene/protein

EBF2

in H9 cells
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44180

gene/protein

WNT3A

NOT affects_expression of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44181

gene/protein

WNT3A

NOT affects_expression of

gene/protein

NANOG

NANOG: marker for pluripotency
Comment Stimulation of H9 cells with Wnt3a expectedly enhanced the top-flash reporter activity and rapidly up-regulated expression of MIXL1, T gene, PITX2, and EBF2. There were no effects on POU5F1, NANOG, and SOX2.
Formal Description
Interaction-ID: 44182

gene/protein

WNT3A

NOT affects_expression of

gene/protein

SOX2

SOX2: marker for pluripotency
Comment In response to rapamycin treatment, H9 cells up-regulated gene expression of CCNG2 (which encodes Cyclin G2) and programmed cell death 4 (PDCD4), both of which inhibit cell proliferation.
Formal Description
Interaction-ID: 44187

drug/chemical compound

Rapamycin

increases_expression of

gene/protein

PDCD4

in H9 cells
Comment In response to rapamycin treatment, H9 cells up-regulated gene expression of CCNG2 (which encodes Cyclin G2) and programmed cell death 4 (PDCD4), both of which inhibit cell proliferation.
Formal Description
Interaction-ID: 44192

gene/protein

PDCD4

decreases_activity of

in H9 cells
Comment In response to rapamycin treatment, H9 cells up-regulated gene expression of CCNG2 (which encodes Cyclin G2) and programmed cell death 4 (PDCD4), both of which inhibit cell proliferation.
Formal Description
Interaction-ID: 44194

gene/protein

CCNG2

decreases_activity of

in H9 cells
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44215

gene/protein

PDCD4

affects_activity of

process

cell growth

Overexpression of PDCD4 markedly reduced cell growth.
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44216

gene/protein

CCNG2

NOT affects_expression of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44217

gene/protein

CCNG2

NOT affects_expression of

gene/protein

SOX2

SOX2: marker for pluripotency
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44218

gene/protein

PDCD4

NOT affects_expression of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44219

gene/protein

PDCD4

NOT affects_expression of

gene/protein

SOX2

SOX2: marker for pluripotency
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44220

gene/protein

MTOR

affects_expression of

gene/protein

CCNG2

Cyclin G2 is a downstream target of mTOR in hESCs and regulates cell proliferation.
Drugbank entries Show/Hide entries for MTOR
Comment Overexpression of Cyclin G2 and PDCD4 markedly reduced cell growth (to 53% and 68% of control, respectively) but failed to affect cell morphology or reduce OCT-4 and SOX2 expression. Thus, Cyclin G2 and PDCD4 are downstream targets of mTOR in hESCs and regulate cell proliferation, but not pluripotency.
Formal Description
Interaction-ID: 44221

gene/protein

MTOR

affects_expression of

gene/protein

PDCD4

PDCD4 is a downstream target of mTOR in hESCs and regulates cell proliferation.
Drugbank entries Show/Hide entries for MTOR
Comment The mRNA and protein levels of OCT-4, SOX2, and NANOG were unaltered 36 h after rapamycin treatment, when the transcriptional activity of MIXL1, T gene, PITX2, and EBF2 was already up-regulated.
Formal Description
Interaction-ID: 44223

drug/chemical compound

Rapamycin

NOT affects_expression of

gene/protein

POU5F1

OCT-4: marker for pluripotency
Comment The mRNA and protein levels of OCT-4, SOX2, and NANOG were unaltered 36 h after rapamycin treatment, when the transcriptional activity of MIXL1, T gene, PITX2, and EBF2 was already up-regulated.
Formal Description
Interaction-ID: 44230

drug/chemical compound

Rapamycin

NOT affects_expression of

gene/protein

SOX2

SOX2: marker for pluripotency
Comment The mRNA and protein levels of OCT-4, SOX2, and NANOG were unaltered 36 h after rapamycin treatment, when the transcriptional activity of MIXL1, T gene, PITX2, and EBF2 was already up-regulated.
Formal Description
Interaction-ID: 44231

drug/chemical compound

Rapamycin

NOT affects_expression of

gene/protein

NANOG

NANOG: marker for pluripotency
Comment Treatment of H9 or H1 cells with rapamycin, a bacterial macrolide and a highly specific inhibitor of mTOR, markedly impaired the pluripotency of both cell lines.
Formal Description
Interaction-ID: 44235

drug/chemical compound

Rapamycin

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for MTOR
Comment The Wnt pathway activity was enhanced by mTOR inhibition. Rapamycin rapidly increased luciferase activity in H9 cells transiently transfected with the Top-flash reporter gene, which assesses Wnt/beta-catenin-mediated transcriptional activation.
Formal Description
Interaction-ID: 44903

gene/protein

MTOR

decreases_activity of

in H9 cells
Drugbank entries Show/Hide entries for MTOR