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1996-02-27
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Document 0525
DOCN M9630525
TI Mutational analysis of cell cycle arrest, nuclear localization and
virion packaging of human immunodeficiency virus type 1 Vpr.
DT 9603
AU Di Marzio P; Choe S; Ebright M; Knoblauch R; Landau NR; Aaron Diamond
AIDS Research Center, New York, New York, USA.
SO J Virol. 1995 Dec;69(12):7909-16. Unique Identifier : AIDSLINE
MED/96079040
AB Human immunodeficiency virus type 1 Vpr is a virion-associated,
regulatory protein that is required for efficient viral replication in
monocytes/macrophages. The protein is believed to act in conjunction
with the Gag matrix protein to allow import of the viral preintegration
complex in nondividing cells. In cells, Vpr localizes to the nucleus.
Recently, we showed that Vpr prevents the activation of p34cdc2-cyclin
B. This results in arrest of Vpr-expressing cells in the G2/M phase of
the cell cycle. Here, we use a panel of expression vectors encoding Vpr
molecules mutated in the amino-terminal alpha-helical region, the
central hydrophobic region, or the carboxy-terminal basic region to
define the functional domains of the protein. The results showed cell
cycle arrest was largely controlled by the carboxy-terminal basic domain
of the protein. In contrast, the amino-terminal alpha-helical region of
Vpr was required for nuclear localization and packaging into virions.
The carboxy terminus appeared to be unnecessary for nuclear
localization. In the alpha-helical region, mutation of Ala-30 to Pro
resulted in a protein that localized to the cytoplasm. Surprisingly,
fusion of Vpr to luciferase resulted in a molecule that failed to
localize to the nucleus. In addition, we show that simian
immunodeficiency virus Vpr, but not Vpx, induces G2 arrest. We speculate
that Vpr has two sites for interaction with cellular factors: one in the
alpha-helical region that specifies nuclear localization and one in the
carboxy-terminal domain that is required for Cdc2 inhibition.
DE Amino Acid Sequence Base Sequence *Cell Cycle Cell Line Cell
Nucleus/*VIROLOGY DNA Mutational Analysis DNA Primers Gene Products,
vpr/*BIOSYNTHESIS/CHEMISTRY/PHYSIOLOGY *Genes, vpr Human
HIV-1/GENETICS/*PHYSIOLOGY Immunoblotting Macrophages/VIROLOGY
Molecular Sequence Data Monocytes/VIROLOGY Polymerase Chain Reaction
Protein Structure, Secondary Recombinant Proteins/BIOSYNTHESIS
Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Transfection
Virion/GENETICS/*PHYSIOLOGY *Virus Replication JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).