Identification of ANKRD11 as a p53 coactivator

J Cell Sci. 2008 Nov 1;121(Pt 21):3541-52. doi: 10.1242/jcs.026351. Epub 2008 Oct 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • DNA / chemistry
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Genes, p53
  • HeLa Cells
  • Humans
  • Models, Biological
  • Mutation
  • Promoter Regions, Genetic*
  • Protein Structure, Tertiary
  • Repressor Proteins / metabolism*
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism*


  • ANKRD11 protein, human
  • Repressor Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA