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Tumor Suppressor miR-22 Determines p53-Dependent Cellular Fate through Post-transcriptional Regulation of p21

dangdang 添加于 2011-11-24 21:26 | 1444 次阅读 | 0 个评论

作者
Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, Okabe A, Schetter AJ, Bowman ED, Midorikawa Y, Sugiyama Y, Aburatani H, Harris CC, Nakagama H
摘要
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. Cancer Res; 71(13); 4628–39. ©2011 AACR.
详细资料
- 文献种类:期刊
- 期刊名称: Cancer Research
- 期刊缩写: Cancer Research
- 期卷页: 2011年第71卷第13期 4628-4639页
- ISBN: 0008-5472
标签

miR22
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