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Identification of ANKRD11 as a p53 coactivator

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dc.contributor.authorNeilsen, P.
dc.contributor.authorCheney, K.
dc.contributor.authorLi, C.
dc.contributor.authorChen, D.
dc.contributor.authorNoll, J.
dc.contributor.authorSchulz, R.
dc.contributor.authorPowell, J.
dc.contributor.authorKumar, R.
dc.contributor.authorCallen, D.
dc.date.issued2008
dc.description.abstractThe 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.
dc.description.statementofresponsibilityPaul 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
dc.identifier.citationJournal of Cell Science, 2008; 121(21):3541-3552
dc.identifier.doi10.1242/jcs.026351
dc.identifier.issn0021-9533
dc.identifier.issn1477-9137
dc.identifier.orcidNoll, J. [0000-0001-7375-635X]
dc.identifier.orcidCallen, D. [0000-0002-6189-9991]
dc.identifier.urihttp://hdl.handle.net/2440/52397
dc.language.isoen
dc.publisherCompany of Biologists Ltd
dc.source.urihttps://doi.org/10.1242/jcs.026351
dc.subjectAcetylation
dc.subjectAnkyrin repeat domain protein
dc.subjectBreast cancer
dc.subjectp53
dc.subjectp53 mutant rescue
dc.titleIdentification of ANKRD11 as a p53 coactivator
dc.typeJournal article
pubs.publication-statusPublished

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