Von Hippel Lindau Binding Protein 1-mediated Degradation of Integrase Affects HIV-1 Gene Expression at a Postintegration Step

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Aug 19

PMID 17698809

Citations 51

Authors

Aurelie Mousnier

Nicole Kubat

Aurelie Massias-Simon

Emmanuel Segeral

Jean-Christophe Rain

Richard Benarous

Stephane Emiliani

Catherine Dargemont

Affiliations

Soon will be listed here.

Abstract

HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin-proteasome pathway. Here, we identify von Hippel-Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integration-transcription transition of the viral replication cycle.

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