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

Laura D. Shostak, John Ludlow, Jennifer Fisk, Shannon Pursell, Bobbie J. Rimel, Don Nguyen, Joseph D. Rosenblatt, Vicente Planelles

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Abstract

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 G2 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 G2 arrest. After G2 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.

Original languageEnglish (US)
Pages (from-to)156-165
Number of pages10
JournalExperimental Cell Research
Volume251
Issue number1
DOIs
StatePublished - Aug 25 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Shostak, L. D., Ludlow, J., Fisk, J., Pursell, S., Rimel, B. J., Nguyen, D., Rosenblatt, J. D., & Planelles, V. (1999). Roles of p53 and caspases in the induction of cell cycle arrest and apoptosis by HIV-1 vpr. Experimental Cell Research, 251(1), 156-165. https://doi.org/10.1006/excr.1999.4568