Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr.
The effects of HIV-1 encoded proteins NCp7, vpr and NCp7:vpr complex on the activity of protein phosphatase-2A0 have been tested. We report that NCp7 is an activator of protein phosphatase-2A0 and that vpr activated protein phosphatase-2A0 only slightly. We also report that NCp7 and vpr form a tight complex which becomes a more potent activator of protein phosphatase-2A0 than NCp7 alone. The ability of NCp7 to activate protein phosphatase-2A0 is regulated by vpr. The C-terminal portion of vpr prevents NCp7 from activating protein phosphatase-2A0 while the N-terminal portion of vpr potentiates the effect of NCp7 on the activity of protein phosphatase-2A0. Our findings indicate that vpr may be acting as a targeting subunit which directs NCp7 to activate protein phosphatase-2A0. In view of the fact that protein phosphatase-2A functions as an inhibitor of G0 to M transition of the cell cycle and is involved in other key cellular processes such as the control of RNA transcription, the results presented in this report may explain how HIV-1 causes cell cycle arrest which may lead to CD4+ T cell depletion and also how it disturbs normal cellular processes of its host cell.
Tung
H Y
HY
Laboratoire de Physiologie de la Reproduction, CNRS URA 1449, INRA, Université Pierre et Marie Curie, Paris, France. ltung@hall.snv.jussieu.fr
De Rocquigny
H
H
Zhao
L J
LJ
Cayla
X
X
Roques
B P
BP
Ozon
R
R
D000818:Animals; D002213:Capsid / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins; D004789:Enzyme Activation; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D013552:Swine; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D036022:Capsid Proteins; D015683:Gene Products, gag; D016336:Gene Products, vpr; C071884:NCP7 protein, Human immunodeficiency virus 1; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2