Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain is essential for Vpu-mediated ER degradation of CD4

Virology
M Paul, M A Jabbar

Abstract

Human immunodeficiency virus type 1 (HIV-1) Vpu is phosphorylated at two serine residues (Ser52 and Ser56) present within the acidic dodecapeptide region of the 54-aa cytoplasmic domain. Previous experiments have shown that Vpu phosphorylation is critical for the degradation of CD4 in the endoplasmic reticulum. In this study, we carried out experiments to elucidate the role of individual phosphoacceptor sites in CD4 proteolysis. We show here that acidic amino acids could not functionally substitute for phosphoserines in Vpu that is capable of inducing the degradation of CD4. Our studies have further revealed that phosphorylation of either of the two phosphoacceptor sites is not sufficient to generate a functional Vpu protein. When tested for functional complementation, inactive phosphorylation-proficient Vpu mutants failed to generate Vpu proteins that had the ability to induce the degradation of Vpu-sensitive glycoproteins. The failure to complement was not due to assembly defects in the Vpu protein as unphosphorylated Vpu formed oligomeric complexes in the cell. We also showed that Vpu expression inhibits protein transport in a phosphorylation-dependent manner. Our studies have thus revealed that both phosphoserines in Vpu ar...Continue Reading

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Citations

Aug 1, 1998·AIDS Research and Human Retroviruses·F Bibollet-RucheM Peeters
Dec 1, 2009·Journal of Translational Medicine·Samuele E BurasteroLucia Lopalco
Dec 24, 2010·Retrovirology·Mathieu DubéÉric A Cohen
Jan 28, 2010·Retrovirology·Ilias ChristodoulopoulosPaula M Cannon
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S HatakeyamaK Nakayama
Jul 20, 2012·Molecular Biology International·Jason HammondsPaul Spearman
Jan 13, 2012·The Protein Journal·Marcos Vinícius Pereira GondimEnrique Roberto Argañaraz
Jun 3, 2000·Annual Review of Immunology·D TortorellaH L Ploegh
Sep 23, 2010·Molecular Aspects of Medicine·Amy Andrew, Klaus Strebel
Aug 2, 2008·Microbes and Infection·Masako NomaguchiAkio Adachi
Oct 12, 1999·Biopolymers·B BechingerS Schinzel
Jun 20, 2015·PLoS Genetics·Theresa B LovelessDavid P Toczyski
Jul 1, 2016·Microbiology and Molecular Biology Reviews : MMBR·Guangdi Li, Erik De Clercq
Nov 24, 2004·The Journal of Biological Chemistry·Palakurthy Rajendra KumarSundarasamy Mahalingam
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gangadhara SailajaAbdul M Jabbar

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