       Document 0408
 DOCN  M9620408
 TI    Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells
       in the G2 phase of the cell cycle by inhibiting p34cdc2 activity.
 DT    9602
 AU    He J; Choe S; Walker R; Di Marzio P; Morgan DO; Landau NR; Aaron Diamond
       AIDS Research Center, New York, New York 10016,; USA.
 SO    J Virol. 1995 Nov;69(11):6705-11. Unique Identifier : AIDSLINE
       MED/96013763
 AB    The Vpr accessory gene product of human immunodeficiency virus types 1
       and 2 and simian immunodeficiency virus is believed to play a role in
       permitting entry of the viral core into the nucleus of nondividing
       cells. A second role for Vpr was recently suggested by Rogel et al. (M.
       E. Rogel, L. I. Wu, and M. Emerman, J. Virol. 69:882-888, 1995), who
       showed that Vpr prevents the establishment in vitro of chronically
       infected HIV producer cell lines, apparently by causing infected cells
       to arrest in the G2/M phase of the cell cycle. In cycling cells,
       progression from G2 to M phase is driven by activation of the
       p34cdc2/cyclin B complex, an event caused, in part, by dephosphorylation
       of two regulatory amino acids of p34cdc2 (Thr-14 and Tyr-15). We show
       here that Vpr arrests the cell cycle in G2 by preventing the activation
       of the p34cdc2/cyclin B complex. Vpr expression in cells caused p34cdc2
       to remain in the phosphorylated, inactive state, p34cdc2/cyclin B
       complexes immunoprecipitated from cells expressing Vpr were almost
       completely inactive in a histone H1 kinase assay. Coexpression of a
       constitutively active mutant p34cdc2 molecule with Vpr relieved the G2
       arrest. These findings strongly suggest that Vpr arrests cells in G2 by
       preventing the activation of the p34cdc2/cyclin B complex that is
       required for entry into M phase. In vivo, Vpr might, by preventing
       p34cdc2 activation, delay or prevent apoptosis of infected cells. This
       would increase the amount of virus each infected cell produced.
 DE    *Cell Cycle  Cell Line  Comparative Study  Enzyme Activation  Gene
       Expression  Gene Products, vpr/*BIOSYNTHESIS/METABOLISM  G2 Phase  Hela
       Cells  Human  HIV-1/GENETICS/*PHYSIOLOGY  Kinetics  Mitosis  Protein
       p34cdc2/*ANTAGONISTS & INHIB/METABOLISM  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  SIV/PHYSIOLOGY  Time Factors  Transfection
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

