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.
Mahalingam
S
S
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ayyavoo
V
V
Patel
M
M
Kieber-Emmons
T
T
Kao
G D
GD
Muschel
R J
RJ
Weiner
D B
DB
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000235:genetics; D016195:G2 Phase / Q000235:genetics*; D005786:Gene Expression Regulation; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D011506:Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D016336:Gene Products, vpr; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; C072621:Psmd7 protein, mouse