Document Detail

A carboxy-terminally truncated form of the human immunodeficiency virus type 1 Vpr protein induces apoptosis via G(1) cell cycle arrest.
MedLine Citation:
PMID:  10846089     Owner:  NLM     Status:  MEDLINE    
Viral protein R (Vpr) of human immunodeficiency virus type 1 inhibits cell proliferation by arresting the cell cycle at the G(2) phase and inducing to apoptosis after G(2) arrest. We have reported previously that C81, a carboxy-terminally truncated form of Vpr, interferes with cell proliferation via a novel pathway that is distinct from G(2) arrest. However, the mechanism of this effect of C81 is unknown. We demonstrate here that C81 can induce apoptosis via G(1) arrest of the cell cycle. Immunostaining for various markers of stages of the cell cycle and flow cytometry analysis of DNA content showed that most HeLa cells that had been transiently transfected with a C81 expression vector were arrested at the G(1) phase and not at the G(2) or S phase of the cell cycle. Staining for annexin V, which binds phosphatidylserine on the plasma membrane, as an early indicator of apoptosis and measurement of the activity of caspase-3, a signaling molecule in apoptotic pathways, indicated that C81 is a strong inducer of apoptosis. Expression of C81 induced the condensation, fragmentation, and clumping of chromatin that are typical of apoptosis. Furthermore, the kinetics of the C81-induced G(1) arrest were closely correlated with changes in the number of annexin V-positive cells and the activity of caspase-3. Replacement of Ile or Leu residues by Pro at positions 60, 67, 74, and 81 within the leucine zipper-like domain of C81 revealed that Ile60, Leu67, and Ile74 play important roles both in the C81-induced G(1) arrest and in apoptosis. Thus, it appears that C81 induces apoptosis through pathways that are identical to those utilized for G(1) arrest of the cell cycle. It has been reported that Ile60, Leu67, and Ile74 also play an important role in the C81-induced suppression of growth. These results suggest that the suppression of growth induced by C81 result in apoptosis that is independent of G(2) arrest of the cell cycle.
M Nishizawa; M Kamata; R Katsumata; Y Aida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of virology     Volume:  74     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6058-67     Citation Subset:  IM; X    
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Ibaraki 305-0074, Japan.
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MeSH Terms
G1 Phase
Gene Products, vpr / genetics,  metabolism*
HIV-1 / genetics,  metabolism*
Hela Cells
Isoleucine / genetics,  metabolism
Leucine / genetics,  metabolism
Leucine Zippers
Sequence Deletion
vpr Gene Products, Human Immunodeficiency Virus
Reg. No./Substance:
0/Gene Products, vpr; 0/vpr Gene Products, Human Immunodeficiency Virus; 61-90-5/Leucine; 73-32-5/Isoleucine

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