miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42.
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.
Park
Seong-Yeon
SY
National Creative Research Center and School of Biological Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea.
Lee
Jung Hyun
JH
Ha
Minju
M
Nam
Jin-Wu
JW
Kim
V Narry
VN
D017209:Apoptosis; D002470:Cell Survival; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016158:Genes, p53; D006367:HeLa Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*
D035683:MicroRNAs; D034741:RNA, Small Interfering; D008156:Luciferases; D020764:cdc42 GTP-Binding Protein