Document Detail


Oct1 is required for mTOR-induced G1 cell cycle arrest via the control of p27(Kip1) expression.
MedLine Citation:
PMID:  20935455     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Oct1 is a ubiquitously expressed transcription factor that is induced in response to DNA damage to modulate gene expression. Herein, Oct1 deficient mouse embryonic fibroblasts were used as a model to study the importance of Oct1 in cellular stress response. Cells lacking Oct1 kept proliferating and bypassed the G(1) cell cycle arrest induced by glucose or amino acid starvation. Indeed, mTOR-mediated regulation of proliferation was abolished in Oct1(-/-) cells starved for glucose or amino acids and Oct1(-/-) cells were also insensitive to mTOR inhibition by rapamycin. Furthermore, in wild-type cells, Oct1 controls the transcription of the CDK inhibitor p27(Kip1) downstream of the mTOR pathway and Oct1-null cells failed to upregulate p27(Kip1) in response to rapamycin or glucose starvation. p27(Kip1) is required for rapamycin or nutrient starvation-induced G(1)-arrest, as p27(-/-) fibroblasts were largely insensitive to rapamycin treatment or glucose starvation. Thus, Oct1 appears to be a critical mediator of the growth arrest induced by mTOR inhibition via the control of p27(Kip1) expression.
Authors:
Mathieu Dalvai; Karin Schubart; Arnaud Besson; Patrick Matthias
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-26
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3933-44     Citation Subset:  IM    
Affiliation:
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrase, Basel, Switzerland. Mathieu.dalvai@ibcg.biotoul.fr
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