HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle
HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle
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DOI：
10.1073/pnas.95.7.3419
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发表时间：
1998-03-31
影响因子：
11.1
通讯作者：
Weiner, DB
中科院分区：
文献类型：
--
作者：
Mahalingam, S;Ayyavoo, V;Weiner, DB
HIV-1辅助基因产物Vpr具有多种重要的功能，包括将HIV逆转录复合物导入非分裂细胞的核内、细胞分化（包括细胞周期停滞在G（2）/M期边界）、免疫抑制和增强病毒复制。用酵母双杂交技术鉴定了人Vpr相互作用蛋白（hVIP/MOV 34），该基因与同时鉴定的34-kDa人MOV 34同源，MOV 34家族包括作为细胞生长和分化的转录和蛋白水解调节剂的蛋白质。我们证明了推定的配体hVIP/MOV 34和Vpr在体外和体内的直接相互作用。hVIP/MOV 34定位于细胞核，并且似乎作为细胞周期级联的组分起作用。我们观察到Vpr诱导细胞周期停滞在G（2）/M期边界与hVIP/MOV 34亚细胞定位从核定位到核周定位的变化之间的关联，这进一步与成熟促进因子相关的组蛋白HI激酶活性的抑制有关，我们的结论是，hVIP/MOV 34参与调节细胞周期和可能的细胞辅助因子HIV-1 Vpr。
Several important and possibly interrelated functions have been identified for the HIV-1 accessory gene product Vpr, These include import of the HIV reverse transcription complex into the nucleus of nondividing cells, cellular differentiation including cell cycle arrest at the G(2)/M phase border, immune suppression, and enhancement of virus replication, We have cloned a candidate Vpr ligand, termed human Vpr interacting protein (hVIP/MOV34), by using a yeast two-hybrid assay, This gene is homologous to a simultaneously identified 34-kDa human mov34 homologue, The MOV34 family includes proteins that function as transcriptional and proteolytic regulators of cell growth and differentiation. We demonstrate direct interactions between the putative ligand hVIP/MOV34 and Vpr in vitro and in vivo. hVIP/MOV34 localizes to the nucleus and appears to function as a component of the cell cycle cascade. We observe an association between the induction of cell cycle arrest at the G(2)/M phase border by Vpr and a change in the subcellular localization of hVIP/MOV34 from a nuclear to a perinuclear localization, This was further associated with the inhibition of maturation promoting factor-associated histone HI kinase activity, We conclude that hVIP/MOV34 is involved in the regulation of the cell cycle and a likely cellular cofactor for HIV-1 Vpr.