title: 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.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mahalingam
authors.forename: V
authors.initials: V
authors.lastname: Ayyavoo
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: T
authors.initials: T
authors.lastname: Kieber-Emmons
authors.forename: G D
authors.initials: GD
authors.lastname: Kao
authors.forename: R J
authors.initials: RJ
authors.lastname: Muschel
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: 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
chemical_list: 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