Document Detail

Viral infections and cell cycle G2/M regulation.
MedLine Citation:
PMID:  15780175     Owner:  NLM     Status:  MEDLINE    
Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well-characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.
Richard Y Zhao; Robert T Elder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Cell research     Volume:  15     ISSN:  1001-0602     ISO Abbreviation:  Cell Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-22     Completed Date:  2005-12-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9425763     Medline TA:  Cell Res     Country:  China    
Other Details:
Languages:  eng     Pagination:  143-9     Citation Subset:  IM    
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 2120, USA.
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MeSH Terms
CDC2 Protein Kinase / metabolism*
DNA Damage
DNA Replication / physiology
DNA, Viral / physiology
G2 Phase / physiology*
Genes, vpr*
HIV Infections / virology
HIV-1 / genetics,  physiology*
Mitosis / physiology
Schizosaccharomyces / cytology,  physiology
Virus Replication
Grant Support
Reg. No./Substance:
0/DNA, Viral; EC Protein Kinase

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