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https://hdl.handle.net/2440/52397
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Type: | Journal article |
Title: | Identification of ANKRD11 as a p53 coactivator |
Author: | Neilsen, P. Cheney, K. Li, C. Chen, D. Noll, J. Schulz, R. Powell, J. Kumar, R. Callen, D. |
Citation: | Journal of Cell Science, 2008; 121(21):3541-3552 |
Publisher: | Company of Biologists Ltd |
Issue Date: | 2008 |
ISSN: | 0021-9533 1477-9137 |
Statement of Responsibility: | 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 |
DOI: | 10.1242/jcs.026351 |
Published version: | http://dx.doi.org/10.1242/jcs.026351 |
Appears in Collections: | Aurora harvest Medicine publications |
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