von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

Aurélie Mousnier, Nicole Kubat, Aurélie Massias-Simon, Emmanuel Ségéral, Jean-Christophe Rain, Richard Benarous, Stéphane Emiliani, Catherine Dargemont

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13615-20
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number34
DOIs
Publication statusPublished - 21 Aug 2007

Keywords

  • Carrier Proteins
  • Gene Expression Regulation, Viral
  • HIV Integrase
  • HIV-1
  • HeLa Cells
  • Humans
  • Molecular Chaperones
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Transcription, Genetic
  • Ubiquitin-Protein Ligases
  • Virus Internalization

Fingerprint Dive into the research topics of 'von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step'. Together they form a unique fingerprint.

  • Cite this