Histone deacetylases specifically down-regulate p53-dependent gene activation

Li Jung Juan, Wei Jong Shia, Mei Hui Chen, Wen Ming Yang, Edward Seto, Young Sun Lin, Cheng-Wen Wu*

*此作品的通信作者

研究成果: Article同行評審

339 引文 斯高帕斯(Scopus)

摘要

p53, the most commonly mutated gene in cancer cells, directs cell cycle arrest or induces programmed cell death (apoptosis) in response to stress. It has been demonstrated that p53 activity is up-regulated in part by posttranslational acetylation. In agreement with these observations, here we show that mammalian histone deacetylase (HDAC)-1, -2, and -3 are all capable of down-regulating p53 function. Down-regulation of p53 activity by HDACs is HDAC dosage-dependent, requires the deacetylase activity of HDACs, and depends on the region of p53 that is acetylated by p300/CREB-binding protein (CBP). These results suggest that interactions of p53 and HDACs likely result in p53 deacetylation, thereby reducing its transcriptional activity. In support of this idea, GST pull-down and immunoprecipitation assays show that p53 interacts with HDAC1 both in vitro and in vivo. Furthermore, a pre- acetylated p53 peptide was significantly deacetylated by immunoprecipitated wild type HDAC1 but not deacetylase mutant. Also, co-expression of HDAC1 greatly reduced the in vivo acetylation level of p53. Finally, we report that the activation potential of p53 on the BAX promoter, a natural p53-responsive system, is reduced in the presence of HDACs. Taken together, our findings indicate that deacetylation of p53 by histone deacetylases is likely to be part of the mechanisms that control the physiological activity of p53.

原文English
頁(從 - 到)20436-20443
頁數8
期刊Journal of Biological Chemistry
275
發行號27
DOIs
出版狀態Published - 7 七月 2000

指紋

深入研究「Histone deacetylases specifically down-regulate p53-dependent gene activation」主題。共同形成了獨特的指紋。

引用此