Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2

	Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2
	Lei, WW; Zhang, KH; Pan, XC; Wang, DM; Hu, Y; Yang, YN; Song, JG
刊名	CELL DEATH & DISEASE
	2010
卷号	1 期号:1 页码:e44-e44
关键词	apoptosis HDAC1 HDAC2 TGF-beta 1 ERK1/2 signalling
通讯作者	Song, JG (reprint author), Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,jgsong@sibs.ac.cn
英文摘要	Histone deacetylases (HDACs) are epigenetic regulators that are important for the control of various pathophysiological events. We found that HDAC inhibitors completely abolished transforming growth factor-beta 1 (TGF-beta 1)-induced apoptosis in AML-12 and primary mouse hepatocytes. Expression of a dominant-negative mutant of HDAC1 or downregulation of HDAC1 by RNAi both suppressed TGF-beta 1-induced apoptosis. In addition, overexpression of HDAC1 enhanced TGF-beta 1-induced apoptosis, and the rescue of HDAC1 expression in HDAC1 RNAi cells restored the apoptotic response of cells to TGF-beta 1. These data indicate that HDAC1 functions as a proapoptotic factor in TGF-beta 1-induced apoptosis. In contrast, downregulation of HDAC2 by RNAi increased spontaneous apoptosis and markedly enhanced TGF-beta 1-induced apoptosis, suggesting that HDAC2 has a reciprocal role in controlling cell survival. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) by MEK1 inhibitor PD98059 or expression of a kinase-dead mutant of MEK1 restored the apoptotic response to TGF-beta 1 in HDAC1 RNAi cells. Strikingly, HDAC2 RNAi caused an inhibition of ERK1/2, and the spontaneous apoptosis can be abolished by reactivation of ERK1/2. Taken together, our data demonstrate that HDAC1 and 2 reciprocally affect cell viability by differential regulation of ERK1/2; these observations provide insight into the roles and potential mechanisms of HDAC1 and 2 in apoptosis. Cell Death and Disease (2010) 1, e44; doi:10.1038/cddis.2010.21; published online 20 May 2010 Subject Category: Cancer
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	GROWTH-FACTOR-BETA ; TO-MESENCHYMAL TRANSITION ; HEPATOMA-CELL LINE ; TGF-BETA ; TRANSFORMING GROWTH-FACTOR-BETA-1 ; MAP KINASES ; PROLIFERATION ; ACTIVATION ; INHIBITORS ; PATHWAY
收录类别	SCI
语种	英语
WOS记录号	WOS:000279818500005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1109]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lei, WW,Zhang, KH,Pan, XC,et al. Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2[J]. CELL DEATH & DISEASE,2010,1(1):e44-e44.
APA	Lei, WW.,Zhang, KH.,Pan, XC.,Wang, DM.,Hu, Y.,...&Song, JG.(2010).Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2.CELL DEATH & DISEASE,1(1),e44-e44.
MLA	Lei, WW,et al."Histone deacetylase 1 and 2 differentially regulate apoptosis by opposing effects on extracellular signal-regulated kinase 1/2".CELL DEATH & DISEASE 1.1(2010):e44-e44.