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RETRACTED: Human immunodeficiency virus type 1 Vpr-mediated G2 cell cycle arrest:: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A (Retracted Article)
被引:49
|作者:
Hrimech, M
Yao, XJ
Branton, PE
Cohen, EA
[1
]
机构:
[1] Univ Montreal, Fac Med, Dept Microbiol & Immunol, Lab Retrovirol Humaine, Montreal, PQ H3C 3J7, Canada
[2] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
来源:
关键词:
cell cycle;
human immunodeficiency virus;
nuclear import;
protein phosphatase 2A;
Vpr;
D O I:
10.1093/emboj/19.15.3956
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The Vpr protein of primate lentiviruses arrests cell cycling at the G(2)/M phase through an inactivation of cyclin B-p34(cdc2) and its upstream regulator cdc25, We provide here biochemical and functional evidence demonstrating that human immunodeficiency virus type 1 (HIV-1) Vpr mediates G(2) arrest by forming a complex with protein phosphatase 2A (PP2A), an upstream regulator of cdc25, Vpr associates with PP2A through a specific interaction with the B55 regulatory subunit, This interaction is necessary but not sufficient for G(2) arrest. Interestingly, we found that Vpr association with B55-containing PP2A targets the enzymatic complex to the nucleus and, importantly, enhances the recruitment and dephosphorylation of the cdc25 substrate. Our data suggest that Vpr mediates G(2) arrest by enhancing the nuclear import of PP2A and by positively modulating its catalytic activity towards active phosphorylated nuclear cdc25.
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页码:3956 / 3967
页数:12
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