S. Mahalingam et al., HIV-1 VPR INTERACTS WITH A HUMAN 34-KDA MOV34 HOMOLOG, A CELLULAR FACTOR LINKED TO THE G(2) M PHASE-TRANSITION OF THE MAMMALIAN-CELL CYCLE/, Proceedings of the National Academy of Sciences of the United Statesof America, 95(7), 1998, pp. 3419-3424
Several important and possibly interrelated functions have been identi
fied 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 replic
ation, We have cloned a candidate Vpr ligand, termed human Vpr interac
ting protein (hVIP/MOV34), by using a yeast two-hybrid assay, This gen
e is homologous to a simultaneously identified 34-kDa human mov34 homo
logue, The MOV34 family includes proteins that function as transcripti
onal and proteolytic regulators of cell growth and differentiation. We
demonstrate direct interactions between the putative ligand hVIP/MOV3
4 and Vpr in vitro and in vivo. hVIP/MOV34 localizes to the nucleus an
d appears to function as a component of the cell cycle cascade. We obs
erve an association between the induction of cell cycle arrest at the
G(2)/M phase border by Vpr and a change in the subcellular localizatio
n 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 co
factor for HIV-1 Vpr.