The role of Vpr in the regulation of HIV-1 gene expression.
Expression of the viral protein R, Vpr, of HIV-1 affects many biological events in host cells including cell cycle progression, and modulates HIV-1 gene transcription. Earlier studies implicating the cellular protein p21(WAF1) (p21) in regulation of HIV-1 transcription, led us to investigate the functional and physical interaction of Vpr and p21. Our results show that Vpr modestly activated HIV-LTR in cells lacking p21 gene. Here, we describe the mechanisms by which p21 and Vpr leading to stimulation of HIV-1 transcription. Data from the protein-protein interaction experiments revealed the ability of Vpr, p21 and p300 to form a complex. Further, we show that, Vpr interacts with the N- and the C-terminal domains of p21. Furthermore, in cells expressing Vpr, p21 localizes to both the cytoplasm and the nucleus. Interestingly, expression of Vpr alleviates p21-mediated inhibition of cell departure from G1 phase. Expression of a mutant Vpr, with arginine 73 altered to serine, did not affect the ability of p21 to cause cells arrest or its sub-cellular localization. These observations reveal a new cellular partner for Vpr, and provide a new therapeutic avenue for controlling HIV-1 expression.
Cui
Jianqi
J
Department of Neuroscience & Center for Neurovirology, Temple University School of Medicine, Temple University, Philadelphia, Pennsylvania 19122, USA.
Tungaturthi
Parithosh K
PK
Ayyavoo
Velpandi
V
Ghafouri
Mohammad
M
Ariga
Hiroyoshi
H
Khalili
Kamel
K
Srinivasan
Alagarsamy
A
Amini
Shohreh
S
Sawaya
Bassel E
BE
D001665:Binding Sites; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D014162:Transfection; D054325:vpr Gene Products, Human Immunodeficiency Virus
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human