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Modulation of HIV‐1 Rev protein abundance and activity by polyubiquitination with unconventional Lys‐33 branching
Author(s) -
Vitte Anne-Laure,
Buchsbaum Samuel,
Jalinot Pierre
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.10.015
Subject(s) - sumo protein , ubiquitin , lysine , mutant , nuclear export signal , cytoplasm , rna , sumo enzymes , chemistry , microbiology and biotechnology , small interfering rna , mutation , nuclear transport , biochemistry , biology , cell nucleus , amino acid , gene
The HIV‐1 Rev protein plays a key role in virus replication by allowing export to the cytoplasm of unspliced or singly‐spliced RNAs. In this report, we investigated whether Rev is modified by ubiquitination or sumoylation. Whereas no evidence of sumoylation was obtained, transient expression experiments showed that ubiquitin conjugates to Rev as high molecular weight polyubiquitin chains. Mutation of the three lysine residues of Rev showed that the site of ubiquitin conjugation is Lys‐115. Experiments with ubiquitin mutants including a single lysine at every seven possible position indicated that branching of the polyubiquitin chains mainly involves Lys‐33. Mutation of Rev Lys‐115 to arginine reduces markedly the steady state amount of the protein, but does not impair its ability to export RNA via the Rev response element. These observations support the notion that polyubiquitination of Rev stabilizes the viral protein but hinders its activity.