| Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by inhibiting the binding of CAND1. | |
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MedLine Citation:
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PMID: 22474075 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The conserved N-terminal domains of the major tegument proteins of herpes viridae encode cysteine proteases with potent ubiquitin and NEDD8 specific deconjugase activity. Here we show that the Epstein-Barr virus (EBV) encoded member of this enzyme family, BPLF1, is targeted to cullin-RING ubiquitin ligases (CRLs) via interaction of the conserved helix-2 with helix-23 of the C-terminal domain (CTD) of cullins, at a site involved in electrostatic interaction with helix-8 of the CRL regulator CAND1. Mutation of the solvent exposed Asp86 and Asp90 of helix-2 to Arg does not affect the enzymatic activity of BPLF1 but abolishes cullin binding and prevents CRL inactivation. Binding of the catalytically active BPLF1 to cullins inhibits the recruitment of CAND1 to the deneddylated CRLs and promotes the selective degradation of cullins by the proteasome. Cullin proteolysis is rescued by overexpression of CAND1 or its CTD-binding N-terminal domain. These findings illustrate a new strategy for viral modulation of CRL activity where the combined effects of cullin deneddylation and their targeting for proteasomal degradation drive stable inactivation of the ligases. |
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Authors:
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Stefano Gastaldello; Simone Callegari; Giuseppe Coppotelli; Sebastian Hildebrand; Moshi Song; Maria G Masucci |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-3 |
Journal Detail:
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Title: Journal of molecular cell biology Volume: - ISSN: 1759-4685 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101503669 Medline TA: J Mol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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