Identification of ANKRD11 as a p53 coactivator
Date
2008
Authors
Neilsen, P.
Cheney, K.
Li, C.
Chen, D.
Noll, J.
Schulz, R.
Powell, J.
Kumar, R.
Callen, D.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Cell Science, 2008; 121(21):3541-3552
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
Conference Name
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.