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- Title
Transcriptional regulation of tumor suppressor p53 by cAMP-responsive element-binding protein/AMP-activated protein kinase complex in response to glucose deprivation.
- Authors
Okoshi, Rintaro; Ando, Kiyohiro; Suenaga, Yusuke; Sang, Meixiang; Kubo, Natsumi; Kizaki, Harutoshi; Nakagawara, Akira; Ozaki, Toshinori
- Abstract
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.
- Subjects
TUMOR suppressor proteins; P53 protein; PROTEIN kinases; APOPTOSIS; CARRIER proteins
- Publication
Genes to Cells, 2009, Vol 14, Issue 12, p1429
- ISSN
1356-9597
- Publication type
Article
- DOI
10.1111/j.1365-2443.2009.01359.x