title: Negative regulation of the p300-p53 interplay by DDX24.
abstract: Numerous studies indicate that p300 acts as a key transcriptional cofactor in vivo, at least, in part, by modulating activities of p53 by acetylation. Nevertheless, the regulation of the p53-p300 interplay is not completely understood. Here, we have identified the DEAD (Asp-Glu-Ala-Asp) box RNA helicase 24 (DDX24) as a novel regulator of the p300-p53 axis. We found that DDX24 interacts with p300, and this interaction leads to suppression of p300-mediated acetylation of p53. Notably, RNA interference-mediated knockdown of endogenous DDX24 significantly increases the acetylation levels of endogenous p53 in human cancer cells and subsequently promotes p53-mediated activation of its transcriptional targets such as p21 and p53 upregulated modulator of apoptosis (PUMA). In contrast, DDX24 expression inhibits the p300-p53 interaction and suppresses p300-mediated acetylation of p53. Moreover, DDX24 is overexpressed in human cancer cells and reduction of DDX24 protein levels by RNA interference induces cell cycle arrest and senescence in a p53-dependent manner. These results reveal DDX24 as an important regulator of p300 and suggest that the modulation of the p53-p300 interplay by DDX24 is critical in controlling p53 activities in human cancer cells.
authors: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
authors: D
authors: D
authors: Shi
authors: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
authors: C
authors: C
authors: Dai
authors: Departments of Biochemistry and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
authors: J
authors: J
authors: Qin
authors: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
authors: W
authors: W
authors: Gu
mesh_terms: D000107:Acetylation; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C412870:DDX24 protein, human; D053487:DEAD-box RNA Helicases