Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line
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Cysteine Proteinase Inhibitors / pharmacology
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HeLa Cells
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Human Immunodeficiency Virus Proteins
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Humans
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Leupeptins / pharmacology
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Mutation
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Phosphorylation
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors
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Transfection
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Ubiquitin / metabolism*
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Viral Regulatory and Accessory Proteins / genetics
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Viral Regulatory and Accessory Proteins / metabolism*
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beta-Transducin Repeat-Containing Proteins / genetics
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beta-Transducin Repeat-Containing Proteins / metabolism*
Substances
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Cysteine Proteinase Inhibitors
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Human Immunodeficiency Virus Proteins
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Leupeptins
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Proteasome Inhibitors
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Ubiquitin
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Viral Regulatory and Accessory Proteins
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beta-Transducin Repeat-Containing Proteins
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vpu protein, Human immunodeficiency virus 1
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Proteasome Endopeptidase Complex
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde