General Information:

Id: 966
Diseases: Amyotrophic lateral sclerosis
Homo sapiens
BTO:0000093 MCF-7 cell
article
Reference: Hu P et al.(2004) Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death J. Biol. Chem. 279 [PMID: 15339911]

Interaction Information:

Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced mRNA expression of two known UPR target genes, viz. the ER resident molecular chaperone BiP (HSPA5) and the transcription factor CHOP (DDIT3).
Formal Description
Interaction-ID: 5954

increases_expression of

gene/protein

HSPA5

Drugbank entries Show/Hide entries for HSPA5
Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced mRNA expression of two known UPR target genes, viz. the ER resident molecular chaperone BiP and the transcription factor CHOP (DDIT3).
Formal Description
Interaction-ID: 5957

increases_expression of

gene/protein

DDIT3

Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced mRNA expression of two known UPR target genes, viz. the ER resident molecular chaperone BiP and the transcription factor CHOP. Phosphorylation of the translation initiation factor eIF2alpha (EIF2S1) also occurred under the same conditions.
Formal Description
Interaction-ID: 5958

increases_phosphorylation of

gene/protein

EIF2S1

Comment Phosphorylation activation of Akt at Ser473 is observed at 2 h with thapsigargin and at 4 h with tunicamycin. Thapsigargin and tunicamycin are ER stressors.
Formal Description
Interaction-ID: 5960

increases_phosphorylation of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment Phosphorylation activation of Akt at Ser473 is observed at 2 h with thapsigargin and at 4 h with tunicamycin. Thapsigargin and tunicamycin are ER stressors.
Formal Description
Interaction-ID: 5963

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment Activation of Akt1 in response to ER stressors thapsigargin and tunicamycin is completely blocked by the PI3K inhibitor LY294002. Results reveal that ER stress acutely induces PI3K-mediated Akt activation. Thapsigargin or tunicamycin also acutely induced phosphorylation of Akt in human lung cancer H1299 cells and human prostate cancer PC-3 cells. These results indicate that acute activation of the Akt pathway is a rather general cell response to ER stress.
Formal Description
Interaction-ID: 5964

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment Akt1 protects cells from ER stress-induced cell death. This process is mTOR independent.
Formal Description
Interaction-ID: 5966

gene/protein

AKT1

decreases_activity of

process

cell death

Drugbank entries Show/Hide entries for AKT1
Comment Data indicate that ER stress induces phosphorylation of mTOR in an Akt-dependent manner; however, this is not involved in cell survival.
Formal Description
Interaction-ID: 5969

gene/protein

AKT1

increases_phosphorylation of

gene/protein

MTOR

Drugbank entries Show/Hide entries for AKT1 or MTOR
Comment Data indicate that ER stress induces phosphorylation of mTOR in an Akt-dependent manner; however, this is not involved in cell survival.
Formal Description
Interaction-ID: 5971

gene/protein

MTOR

NOT affects_activity of

process

cell death

Drugbank entries Show/Hide entries for MTOR
Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced the activation and phosphorylation of ERK1/2 (MAPK3 and MAPK1).
Formal Description
Interaction-ID: 5983

increases_activity of

gene/protein

MAPK3

Drugbank entries Show/Hide entries for MAPK3
Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced the activation and phosphorylation of ERK1/2 (MAPK3 and MAPK1).
Formal Description
Interaction-ID: 5984

increases_activity of

gene/protein

MAPK1

Drugbank entries Show/Hide entries for MAPK1
Comment Incubation of human breast cancer MCF-7 cells with the ER stressors thapsigargin and tunicamycin rapidly induced the phosphorylation of JNK (MAPK8).
Formal Description
Interaction-ID: 5985

increases_phosphorylation of

gene/protein

MAPK8

Drugbank entries Show/Hide entries for MAPK8
Comment The MEK1 (MAP2K1) inhibitor U0126 completely inhibited thapsigargin-induced ERK1/2 phosphorylation.
Formal Description
Interaction-ID: 5986

gene/protein

MAP2K1

increases_phosphorylation of

gene/protein

MAPK3

Drugbank entries Show/Hide entries for MAP2K1 or MAPK3
Comment The MEK1 (MAP2K1) inhibitor U0126 completely inhibited thapsigargin-induced ERK1/2 phosphorylation.
Formal Description
Interaction-ID: 5987

gene/protein

MAP2K1

increases_phosphorylation of

gene/protein

MAPK1

Drugbank entries Show/Hide entries for MAP2K1 or MAPK1
Comment The MEK1 (MAP2K1) inhibitor U0126 increased thapsigargin- and tunicamycin-induced cell death in MCF-7 and H1299 cells. These results suggest that activation of the MEK1/ERK pathway is also a cell survival response to resist ER stress.
Formal Description
Interaction-ID: 5988

drug/chemical compound

U0126

decreases_activity of

gene/protein

MAP2K1

Drugbank entries Show/Hide entries for MAP2K1
Comment The MEK1 (MAP2K1) inhibitor U0126 increased thapsigargin- and tunicamycin-induced cell death in MCF-7 and H1299 cells. These results suggest that activation of the MEK1/ERK pathway is also a cell survival response to resist ER stress.
Formal Description
Interaction-ID: 5989

drug/chemical compound

U0126

increases_activity of

process

cell death

Comment Treatment with the PI3K inhibitor LY294002 or downregulation of Akt1 significantly decreased thapsigargin-induced transcription of cIAP-2 (BIRC3) and XIAP, and expression of cIAP-2 and XIAP proteins was also inhibited, as shown by RT-PCR and Western blotting, respectively. These results indicate that the PI3K/Akt survival pathway, not the ERK pathway, increases cIAP-2 and XIAP function by regulating their transcription in response to ER stress.
Formal Description
Interaction-ID: 6099

increases_quantity of

gene/protein

XIAP

Drugbank entries Show/Hide entries for XIAP
Comment Treatment with the PI3K inhibitor LY294002 or downregulation of Akt1 significantly decreased thapsigargin-induced transcription of cIAP-2 (BIRC3) and XIAP, and expression of cIAP-2 and XIAP proteins was also inhibited, as shown by RT-PCR and Western blotting, respectively. These results indicate that the PI3K/Akt survival pathway, not the ERK pathway, increases cIAP-2 and XIAP function by regulating their transcription in response to ER stress.
Formal Description
Interaction-ID: 6101

increases_quantity of

gene/protein

BIRC3

Comment Treatment with the PI3K inhibitor LY294002 or downregulation of Akt1 significantly decreased thapsigargin-induced transcription of cIAP-2 (BIRC3) and XIAP, and expression of cIAP-2 and XIAP proteins was also inhibited, as shown by RT-PCR and Western blotting, respectively. These results indicate that the PI3K/Akt survival pathway, not the ERK pathway, increases cIAP-2 and XIAP function by regulating their transcription in response to ER stress.
Formal Description
Interaction-ID: 6102

gene/protein

AKT1

increases_quantity of

gene/protein

BIRC3

Drugbank entries Show/Hide entries for AKT1
Comment Treatment with the PI3K inhibitor LY294002 or downregulation of Akt1 significantly decreased thapsigargin-induced transcription of cIAP-2 (BIRC3) and XIAP, and expression of cIAP-2 and XIAP proteins was also inhibited, as shown by RT-PCR and Western blotting, respectively. These results indicate that the PI3K/Akt survival pathway, not the ERK pathway, increases cIAP-2 and XIAP function by regulating their transcription in response to ER stress.
Formal Description
Interaction-ID: 6103

gene/protein

AKT1

increases_quantity of

gene/protein

XIAP

Drugbank entries Show/Hide entries for AKT1 or XIAP