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Cancer Res. 2011 Jul 1;71(13):4628-39. doi: 10.1158/0008-5472.CAN-10-2475. Epub 2011 May 12.

Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21.

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1
Division of Cancer Development System and Cancer Differentiation, National Cancer Center Research Institute, Tsukiji, Japan.

Abstract

Selective activation of p53 target genes in response to various cellular stresses is a critical step in determining the ability to induce cell-cycle arrest or apoptosis. Here we report the identification of the microRNA miR-22 as a p53 target gene that selectively determines the induction of p53-dependent apoptosis by repressing p21. Combinatorial analyses of the AGO2 immunocomplex and gene expression profiles identified p21 as a direct target of miR-22. Induction of p21 was inhibited by miR-22 after exposure to the genotoxic agent Adriamycin (doxorubicin; Bedford Laboratories), sensitizing cells to p53-dependent apoptosis. Interestingly, the activation of miR-22 depended on the intensity of the stresses that induced cells to undergo apoptosis in the presence of p21 suppression. Our findings define an intrinsic molecular switch that determines p53-dependent cellular fate through post-transcriptional regulation of p21.

PMID:
21565979
DOI:
10.1158/0008-5472.CAN-10-2475
[Indexed for MEDLINE]
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