miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42

Nat Struct Mol Biol. 2009 Jan;16(1):23-9. doi: 10.1038/nsmb.1533. Epub 2008 Dec 14.


The tumor suppressor p53 is central to many cellular stress responses. Although numerous protein factors that control p53 have been identified, the role of microRNAs (miRNAs) in regulating p53 remains unexplored. In a screen for miRNAs that modulate p53 activity, we find that miR-29 family members (miR-29a, miR-29b and miR-29c) upregulate p53 levels and induce apoptosis in a p53-dependent manner. We further find that miR-29 family members directly suppress p85 alpha (the regulatory subunit of PI3 kinase) and CDC42 (a Rho family GTPase), both of which negatively regulate p53. Our findings provide new insights into the role of miRNAs in the p53 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Survival
  • Gene Expression Regulation
  • Genes, Reporter
  • Genes, p53*
  • HeLa Cells / cytology
  • HeLa Cells / physiology
  • Humans
  • Luciferases / genetics
  • MicroRNAs / genetics*
  • Plasmids
  • RNA, Small Interfering / genetics*
  • Transfection
  • cdc42 GTP-Binding Protein / genetics*


  • MicroRNAs
  • RNA, Small Interfering
  • Luciferases
  • cdc42 GTP-Binding Protein