Park Seong-Yeon, Lee Jung Hyun, Ha Minju, Nam Jin-Wu, Kim V Narry
National Creative Research Center and School of Biological Sciences, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, South Korea.
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.
肿瘤抑制因子p53在许多细胞应激反应中起核心作用。尽管已经鉴定出许多控制p53的蛋白质因子，但微小RNA（miRNA）在调节p53中的作用仍未被探索。在一项筛选调节p53活性的miRNA的研究中，我们发现miR-29家族成员（miR-29a、miR-29b和miR-29c）以上调p53水平并以p53依赖的方式诱导细胞凋亡。我们进一步发现，miR-29家族成员直接抑制p85α（PI3激酶的调节亚基）和CDC42（一种Rho家族GTP酶），这两者均对p53起负调节作用。我们的研究结果为miRNA在p53途径中的作用提供了新的见解。
