Document Detail


NFκB and ubiquitination: partners in disarming RIPK1-mediated cell death.
MedLine Citation:
PMID:  22477525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanisms regulating cell survival and thus its corollary, cell death, have been intensively studied over the last two decades. Recent studies have shed new light into how non-degradative ubiquitination of the kinase RIPK1 is critical in determining this cell fate. In this review, we summarize recent findings on how ubiquitination of RIPK1 constitutes a survival signal through both NFκB-independent and NFκB-dependent mechanisms. However, in the absence of ubiquitination, RIPK1 becomes a death-signaling molecule capable of engaging both the caspase-dependent apoptosis machinery and the recently described RIPK3-dependent necroptosis machinery. Another layer of complexity is now emerging in that components of the ubiquitin-modifying machinery are themselves regulated by proteolytic processing. This survival/death regulatory mechanism has been best analyzed in the context of TNF receptor signaling, but it is likely that principles learned from TNFR may be applicable to other immune receptors including the antigen and Toll-like receptors.
Authors:
Marie Anne O'Donnell; Adrian T Ting
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunologic research     Volume:  54     ISSN:  1559-0755     ISO Abbreviation:  Immunol. Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2013-03-07     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  8611087     Medline TA:  Immunol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  214-26     Citation Subset:  IM    
Affiliation:
Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. marie.a.odonnell@mssm.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspase 8 / metabolism
Cell Death / physiology*
Cysteine Endopeptidases / metabolism
Humans
NF-kappa B / metabolism*
Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
Ubiquitination
Grant Support
ID/Acronym/Agency:
AI052417/AI/NIAID NIH HHS; R01 AI052417/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; EC 2.7.11.1/RIPK1 protein, human; EC 2.7.11.1/Receptor-Interacting Protein Serine-Threonine Kinases; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Cysteine Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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