Yedavalli Venkat S R K, Shih Hsiu-Ming, Chiang Yu-Ping, Lu Chun-Yi, Chang Luan-Yin, Chen Mao-Yuan, Chuang Che-Yen, Dayton Andrew I, Jeang Kuan-Teh, Huang Li-Min
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institutes of Allergy and Infectious Diseases, Maryland 20892-0460, USA.
J Virol. 2005 Nov;79(21):13735-46. doi: 10.1128/JVI.79.21.13735-13746.2005.
Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr.
1型人类免疫缺陷病毒的病毒蛋白R(Vpr)是病毒发病机制所必需的,并且通过激活半胱天冬酶3和半胱天冬酶9以及扰乱线粒体膜电位参与T细胞凋亡。为了更好地理解Vpr与线粒体的相互作用,我们在此报告鉴定抗凋亡线粒体蛋白HAX-1为一种新的Vpr靶点。我们表明Vpr和HAX-1在物理上相互关联。Vpr在细胞中的过表达使HAX-1从其在线粒体中的正常位置移位,导致线粒体不稳定和细胞死亡。相反,HAX-1的过表达抑制了Vpr的促凋亡活性。