p300 对 RASSF2A 的激活通过组蛋白超乙酰化诱导晚期细胞凋亡。

Activation of RASSF2A by p300 induces late apoptosis through histone hyperacetylation.

机构信息

School of Life Science, Northeast Normal University, Changchun 130024, Peoples Republic of China.

出版信息

Cell Biol Int. 2010 Dec;34(12):1133-9. doi: 10.1042/CBI20090388.

DOI:10.1042/CBI20090388

PMID:20716062

Abstract

Both RASSF2A (Ras-associated family 2A) and p300 are implicated in apoptosis. However, little is known about the interrelationship between these two proteins in induction of apoptosis. Here we show that p300 was able to induce late apoptosis through up-regulation of RASSF2A in human gastric cancer cells SGC-7901 (p53-mutant). Our data demonstrated that p300 stimulated RASSF2A expression in 293T cells in cooperation with the transcription factor Sp1. Results of ChIP (chromatin immunoprecipitation) assays revealed that p300 induced histones H3 and H4 hyperacetylation at RASSF2A promoter. Moreover, p300 and Sp1 reciprocally facilitated their binding to RASSF2A promoter. Overall, data arising from this study indicate that Sp1-mediated RASSF2A gene transcription is activated by p300 through histone acetylation, and this activation plays an important role in inducing late apoptosis.

摘要

RASSF2A（Ras 相关家族 2A）和 p300 都与细胞凋亡有关。然而，关于这两种蛋白在诱导细胞凋亡过程中的相互关系，人们知之甚少。本研究显示，p300 能够通过上调人胃癌细胞 SGC-7901（p53 突变体）中的 RASSF2A 诱导晚期细胞凋亡。我们的数据表明，p300 能够与转录因子 Sp1 协同作用，在 293T 细胞中刺激 RASSF2A 的表达。染色质免疫沉淀（ChIP）实验结果表明，p300 诱导 RASSF2A 启动子处组蛋白 H3 和 H4 的过度乙酰化。此外，p300 和 Sp1 相互促进它们与 RASSF2A 启动子的结合。总的来说，本研究的数据表明，Sp1 介导的 RASSF2A 基因转录被 p300 通过组蛋白乙酰化激活，这种激活在诱导晚期细胞凋亡中发挥重要作用。