Involvement of the betaTrCP in the ubiquitination and stability of the HIV-1 Vpu protein.
The human immunodeficiency virus type 1 (HIV-1) Vpu protein binds to the CD4 receptor and targets it to the proteasome for degradation. This process requires the recruitment of human betaTrCP, a component of the Skp1-Cullin-F box (SCF) ubiquitin ligase complex, that interacts with phosphorylated Vpu molecules. Vpu, unlike other ligands of betaTrCP, has never been reported to be degraded. We provide evidence that Vpu, itself, is ubiquitinated and targeted for degradation by the proteasome. We demonstrate that the mutant Vpu2.6, which cannot interact with betaTrCP, is stable and, unlike wild-type Vpu, is not polyubiquitinated. These results suggest that betaTrCP is involved in Vpu polyubiquitination.
Belaïdouni
Nadia
N
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Marchal
Christelle
C
Benarous
Richard
R
Besnard-Guérin
Corinne
C
D015153:Blotting, Western; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D015853:Cysteine Proteinase Inhibitors; D054298:Human Immunodeficiency Virus Proteins; D007976:Leupeptins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D054334:Viral Regulatory and Accessory Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde