Premium
Transcriptional regulation of tumor suppressor p53 by cAMP‐responsive element‐binding protein/AMP‐activated protein kinase complex in response to glucose deprivation
Author(s) -
Okoshi Rintaro,
Ando Kiyohiro,
Suenaga Yusuke,
Sang Meixiang,
Kubo Natsumi,
Kizaki Harutoshi,
Nakagawara Akira,
Ozaki Toshinori
Publication year - 2009
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2009.01359.x
Subject(s) - creb , transactivation , biology , cyclic amp response element binding protein , creb1 , response element , gene knockdown , transcription factor , protein kinase a , creb binding protein , microbiology and biotechnology , promoter , kinase , gene expression , gene , biochemistry
Tumor suppressor p53 plays a pivotal role in the regulation of cell fate determination in response to a variety of cellular stress including carbon source depletion. In this study, we found that cAMP‐responsive element‐binding protein (CREB) collaborates with AMP‐activated protein kinase α (AMPKα) to regulate the transcription of p53 . Luciferase reporter assays showed that the genomic fragment spanning from −531 to −239 of human p53 gene is required for the transactivation of p53 in response to glucose deprivation. Within this region, we found out a putative CREB‐binding site. siRNA‐mediated knockdown of CREB resulted in a significant inhibition of the up‐regulation of p53 and apoptosis under glucose deprivation. Consistent with these observations, glucose deprivation induced the transcription of p53 and CREB . Additionally, glucose deprivation led to an efficient recruitment of CREB onto the promoter region of p53 gene carrying the canonical CREB‐binding site, indicating that CREB has an ability to bind to the promoter region of p53 gene and transactivate p53 . Furthermore, the amounts of CREB/phospo‐AMPKα complex increased in response to glucose deprivation. Taken together, our present findings suggest that p53 is transcriptionally regulated by CREB/phospho‐AMPKα complex and thereby contributing to the induction of apoptosis under carbon source depletion.