| Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. | |
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MedLine Citation:
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PMID: 21145488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The intimate relationship between mediators of the ubiquitin (Ub)-signaling system and human diseases has sparked profound interest in how Ub influences cell death and survival. While the consequence of Ub attachment is intensely studied, little is known with regards to the effects of other Ub-like proteins (UBLs), and deconjugating enzymes that remove the Ub or UBL adduct. Systematic in vivo RNAi analysis identified three NEDD8-specific isopeptidases that, when knocked down, suppress apoptosis. Consistent with the notion that attachment of NEDD8 prevents cell death, genetic ablation of deneddylase 1 (DEN1) suppresses apoptosis. Unexpectedly, we find that Drosophila and human inhibitor of apoptosis (IAP) proteins can function as E3 ligases of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Finally, we demonstrate that DEN1 reverses this effect by removing the NEDD8 modification. Altogether, our findings indicate that IAPs not only modulate cellular processes via ubiquitylation but also through attachment of NEDD8, thereby extending the complexity of IAP-mediated signaling. |
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Authors:
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Meike Broemer; Tencho Tenev; Kristoffer T G Rigbolt; Sophie Hempel; Blagoy Blagoev; John Silke; Mark Ditzel; Pascal Meier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 40 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-01-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 810-22 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Mary-Jean Mitchell Green Building, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK. meike.broemer@icr.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Drosophila / metabolism Endopeptidases / metabolism Inhibitor of Apoptosis Proteins / genetics, metabolism* RNA Interference* Ubiquitin / genetics, metabolism* Ubiquitin-Protein Ligases / genetics*, metabolism Ubiquitination |
| Chemical | |
Reg. No./Substance:
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0/Inhibitor of Apoptosis Proteins; 0/Ubiquitin; EC 3.4.-/Endopeptidases; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
Comment In:
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Dev Cell. 2010 Dec 14;19(6):791-2
[PMID:
21145494
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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