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.
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 G2/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 G2/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 H1 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.
Mesh Terms:
Amino Acid Sequence, Cell Cycle, G2 Phase, Gene Expression Regulation, Gene Products, vpr, HeLa Cells, Humans, Mitosis, Molecular Sequence Data, Proteins, RNA-Binding Proteins, Recombinant Proteins, Retroviridae Proteins, Transcription, Genetic
Amino Acid Sequence, Cell Cycle, G2 Phase, Gene Expression Regulation, Gene Products, vpr, HeLa Cells, Humans, Mitosis, Molecular Sequence Data, Proteins, RNA-Binding Proteins, Recombinant Proteins, Retroviridae Proteins, Transcription, Genetic
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 31, 1998
PubMed ID: 9520381
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