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|Title:||Identification of ANKRD11 as a p53 coactivator|
|Citation:||Journal of Cell Science, 2008; 121(21):3541-3552|
|Publisher:||Company of Biologists Ltd|
|Paul M. Neilsen, Kelly M. Cheney, Chia-Wei Li, J. Don Chen, Jacqueline E. Cawrse, Renée B. Schulz, Jason A. Powell, Raman Kumar and David F. Callen|
|Abstract:||The ability of p53 to act as a transcription factor is critical for its function as a tumor suppressor. Ankyrin repeat domain 11, ANKRD11 (also known as ANR11 or ANCO1), was found to be a novel p53-interacting protein that enhanced the transcriptional activity of p53. ANKRD11 expression was shown to be downregulated in breast cancer cell lines. Restoration of ANKRD11 expression in MCF-7 (wild-type p53) and MDA-MB-468 (p53(R273H) mutant) cells suppressed their proliferative and clonogenic properties through enhancement of CDKN1A (p21(waf1)/CIP1) expression. ShRNA-mediated silencing of ANKRD11 expression reduced the ability of p53 to activate CDKN1A expression. ANKRD11 was shown to associate with the p53 acetyltransferases and cofactors, P/CAF and hADA3. Exogenous ANKRD11 expression enhanced the levels of acetylated p53 in both MCF-7 and MDA-MB-468 cells. ANKRD11 enhanced the DNA-binding properties of mutant p53(R273H) to the CDKN1A promoter, suggesting that ANKRD11 can mediate the restoration of normal p53 function in some cancer-related p53 mutations. In addition, ANKRD11 itself was found to be a novel p53 target gene. These findings demonstrate a role for ANKRD11 as a p53 coactivator and suggest the involvement of ANKRD11 in a regulatory feedback loop with p53.|
|Keywords:||Acetylation; Ankyrin repeat domain protein; Breast cancer; p53; p53 mutant rescue|
|Appears in Collections:||Medicine publications|
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