Roles of p53 and caspases in the induction of cell cycle arrest and apoptosis by HIV-1 vpr.

Publisher: Academic Press Country of Publication: United States NLM ID: 0373226 Publication Model: Print Cited Medium: Print ISSN: 0014-4827 (Print) Linking ISSN: 00144827 NLM ISO Abbreviation: Exp Cell Res Subsets: MEDLINE

Publication: Orlando Fl : Academic Press
Original Publication: New York, Academic Press.

Apoptosis*/drug effects ; Cell Cycle*/drug effects ; Cell Cycle*/radiation effects; Caspases/*metabolism ; Gene Products, vpr/*metabolism ; HIV-1/*physiology ; Tumor Suppressor Protein p53/*physiology; Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; COS Cells ; Caspase Inhibitors ; Cell Nucleus/drug effects ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Cell Nucleus/radiation effects ; DNA Damage/drug effects ; DNA Damage/radiation effects ; DNA Fragmentation ; Doxorubicin/pharmacology ; Enzyme Activation ; G2 Phase/drug effects ; G2 Phase/radiation effects ; Gamma Rays ; Gene Products, vpr/genetics ; Genetic Vectors/genetics ; HIV-1/genetics ; Humans ; In Situ Nick-End Labeling ; Mechlorethamine/pharmacology ; Signal Transduction/drug effects ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics ; vpr Gene Products, Human Immunodeficiency Virus

The vpr gene from the human immunodeficiency virus type-1 (HIV-1) encodes a 14-kDa protein that prevents cell proliferation by causing a block in the G(2) phase of the cell cycle. This cellular function of vpr is conserved in evolution because other primate lentiviruses, including HIV-2, SIV(mac), and SIV(agm) encode related genes that also induce G(2) arrest. After G(2) arrest, cells expressing vpr undergo apoptosis. The signaling pathways that result in vpr-induced cell cycle arrest and apoptosis have yet to be determined. The p53 tumor suppressor protein is involved in signaling pathways leading to cell cycle arrest and apoptosis in a variety of cell types. In this work, we examine the potential role of p53 in mediating cell cycle block and/or apoptosis by HIV-1 vpr and demonstrate that both phenomena occur independently of the presence and function of p53. Caspases are common mediators of apoptosis. We examined the potential role of caspases in mediating vpr-induced apoptosis by treating vpr-expressing cells with Boc-D-FMK, a broad spectrum, irreversible inhibitor of the caspase family. Boc-D-FMK significantly reduced the numbers of apoptotic cells induced by vpr. Therefore, we conclude that vpr-induced apoptosis is effected via the activation of caspases.
(Copyright 1999 Academic Press.)

CA09363D United States CA NCI NIH HHS; R29-AI41407 United States AI NIAID NIH HHS

0 (Amino Acid Chloromethyl Ketones)
0 (Caspase Inhibitors)
0 (Gene Products, vpr)
0 (Tumor Suppressor Protein p53)
0 (butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone)
0 (vpr Gene Products, Human Immunodeficiency Virus)
50D9XSG0VR (Mechlorethamine)
80168379AG (Doxorubicin)
EC 3.4.22.- (Caspases)

Date Created: 19990810 Date Completed: 19990914 Latest Revision: 20151119

20221213

10.1006/excr.1999.4568

10438581