Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu.
The HIV-1 protein Vpu counteracts the antiviral activity of the innate restriction factor BST-2/tetherin by a mechanism that partly depends on its interaction with β-TrCP, a substrate adaptor for an SCF (Skp-Cullin 1-F box) E3 ubiquitin ligase complex. This suggests that Vpu stimulates the ubiquitination of BST-2 and that this ... underlies the relief of restriction. Here, we show that Vpu stimulates ubiquitination of BST-2. Mutation of all potential ubiquitination sites in the cytoplasmic domain of BST-2, including lysines, cysteines, serines, and threonines, abrogates Vpu-mediated ubiquitination. However, a serine-threonine-serine sequence specifically mediates the downregulation of BST-2 from the cell surface and the optimal relief of restricted virion release. Serine-threonine ubiquitination of BST-2 is likely part of the mechanism by which Vpu counteracts innate defenses.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, CD, Down-Regulation, GPI-Linked Proteins, HEK293 Cells, HIV-1, Human Immunodeficiency Virus Proteins, Humans, Molecular Sequence Data, Serine, Threonine, Ubiquitin, Viral Regulatory and Accessory Proteins, Virion, Virus Release, beta-Transducin Repeat-Containing Proteins
Amino Acid Sequence, Animals, Antigens, CD, Down-Regulation, GPI-Linked Proteins, HEK293 Cells, HIV-1, Human Immunodeficiency Virus Proteins, Humans, Molecular Sequence Data, Serine, Threonine, Ubiquitin, Viral Regulatory and Accessory Proteins, Virion, Virus Release, beta-Transducin Repeat-Containing Proteins
J. Virol.
Date: Jan. 01, 2011
PubMed ID: 20980512
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