von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step.
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.
Mousnier
Aurélie
A
Institut Jacques Monod, Centre National de la Recherche Scientifique, Universités Paris 6 et 7, F-75251 Paris, France.
Kubat
Nicole
N
Massias-Simon
Aurélie
A
Ségéral
Emmanuel
E
Rain
Jean-Christophe
JC
Benarous
Richard
R
Emiliani
Stéphane
S
Dargemont
Catherine
C
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D015967:Gene Expression Regulation, Viral; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D014158:Transcription, Genetic / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; C108825:VBP1 protein, human; C112806:prefoldin; D044767:Ubiquitin-Protein Ligases; D019427:HIV Integrase; D046988:Proteasome Endopeptidase Complex
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