Upregulation of survivin by HIV-1 Vpr.
The human survivin gene belongs to the family of inhibitor of apoptosis proteins (IAP) and is involved in apoptosis inhibition and regulation of cell division. The survivin gene is the only member of the IAP family whose expression is known to be regulated through the cell cycle. Survivin expression reaches the highest levels during the G(2)/M transition and then is rapidly degraded during the G(1) phase. Here we report that the human immunodeficiency virus type 1 (HIV-1) upregulates Survivin expression via survivin promoter transactivation. Vpr, an HIV-1 accessory protein that induces cell cycle arrest in G(2)/M, is necessary and sufficient for this effect. Blocking Vpr-induced G(2)/M arrest leads to elimination of the survivin promoter transactivation by Vpr. Our results suggest that Survivin may be actively involved in regulating cell viability during HIV-1 infection.
Zhu
Y
Y
Department of Microbiology and Immunology, University of Rochester, Rochester, New York 14642, USA.
Roshal
M
M
Li
F
F
Blackett
J
J
Planelles
V
V
D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival; D016193:G1 Phase; D016195:G2 Phase; D016336:Gene Products, vpr / Q000378:metabolism*; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D015658:HIV Infections; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008957:Models, Genetic; D009363:Neoplasm Proteins; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000077022:Survivin; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
C107489:BIRC5 protein, human; D016336:Gene Products, vpr; D051034:Inhibitor of Apoptosis Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D054325:vpr Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D002110:Caffeine; D008156:Luciferases; D001616:beta-Galactosidase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases