miR-29 miRNAs activate p53 by targeting p85α and CDC42

The transcription factor and tumor suppressor p53 is central to many stress responses and is the target of multiple regulators. The regulatory subunit of PI3 kinase, p85α and CDC42 are now both found to be targets of the miR-29 microRNAs. As p85α and CDC42 are repressors of p53, these miRNAs indirectly activate p53 and thus apoptosis. 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 p85α (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.