Identification of ANKRD11 as a p53 coactivator

Paul M. Neilsen, Kelly M. Cheney, Chia Wei Li, J. Don Chen, Jacqueline E. Cawrse, Renée B. Schulz, Jason A. Powelt, Raman Kumar, David F. Callen

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67 Citations (Scopus)

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 (p53R273H mutant) cells suppressed their proliferative and clonogenic properties through enhancement of CDKN1A (p21waf1/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 p53R273H 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.

Original languageEnglish
Pages (from-to)3541-3552
Number of pages12
JournalJournal of Cell Science
Volume121
Issue number21
DOIs
Publication statusPublished or Issued - 1 Nov 2008
Externally publishedYes

Keywords

  • Acetylation
  • Ankyrin repeat domain protein
  • Breast cancer
  • p53
  • p53 mutant rescue

ASJC Scopus subject areas

  • Cell Biology

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