cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)

cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)

The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors. The molecular mechanisms regulating the ability of the RIP proteins to t...

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Main Authors: Bertrand, Mathieu J. M., Lippens, Saskia, Staes, An, Gilbert, Barbara, Roelandt, Ria, De Medts, Jelle, Gevaert, Kris, Declercq, Wim, Vandenabeele, Peter
Format: Online
Language:English
Published: Public Library of Science 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171409/
id pubmed-3171409
recordtype oai_dc
spelling pubmed-31714092011-09-19 cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4) Bertrand, Mathieu J. M. Lippens, Saskia Staes, An Gilbert, Barbara Roelandt, Ria De Medts, Jelle Gevaert, Kris Declercq, Wim Vandenabeele, Peter Research Article The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors. The molecular mechanisms regulating the ability of the RIP proteins to transduce the stress signals remain poorly understood, but seem to rely only partially on their kinase activities. Recent studies on RIP1 and RIP2 have highlighted the importance of ubiquitination as a key process regulating their capacity to activate downstream signaling pathways. In this study, we found that XIAP, cIAP1 and cIAP2 not only directly bind to RIP1 and RIP2 but also to RIP3 and RIP4. We show that cIAP1 and cIAP2 are direct E3 ubiquitin ligases for all four RIP proteins and that cIAP1 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains. Consistently, we show that repressing cIAP1/2 levels affects the activation of NF-κB that is dependent on RIP1, -2, -3 and -4. Finally, we identified Lys51 and Lys145 of RIP4 as two critical residues for cIAP1-mediated ubiquitination and NF-κB activation. Public Library of Science 2011-09-12 /pmc/articles/PMC3171409/ /pubmed/21931591 http://dx.doi.org/10.1371/journal.pone.0022356 Text en Bertrand et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bertrand, Mathieu J. M.
Lippens, Saskia
Staes, An
Gilbert, Barbara
Roelandt, Ria
De Medts, Jelle
Gevaert, Kris
Declercq, Wim
Vandenabeele, Peter
spellingShingle Bertrand, Mathieu J. M.
Lippens, Saskia
Staes, An
Gilbert, Barbara
Roelandt, Ria
De Medts, Jelle
Gevaert, Kris
Declercq, Wim
Vandenabeele, Peter
cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
author_facet Bertrand, Mathieu J. M.
Lippens, Saskia
Staes, An
Gilbert, Barbara
Roelandt, Ria
De Medts, Jelle
Gevaert, Kris
Declercq, Wim
Vandenabeele, Peter
author_sort Bertrand, Mathieu J. M.
title cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
title_short cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
title_full cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
title_fullStr cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
title_full_unstemmed cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
title_sort ciap1/2 are direct e3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (rip1–4)
description The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors. The molecular mechanisms regulating the ability of the RIP proteins to transduce the stress signals remain poorly understood, but seem to rely only partially on their kinase activities. Recent studies on RIP1 and RIP2 have highlighted the importance of ubiquitination as a key process regulating their capacity to activate downstream signaling pathways. In this study, we found that XIAP, cIAP1 and cIAP2 not only directly bind to RIP1 and RIP2 but also to RIP3 and RIP4. We show that cIAP1 and cIAP2 are direct E3 ubiquitin ligases for all four RIP proteins and that cIAP1 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains. Consistently, we show that repressing cIAP1/2 levels affects the activation of NF-κB that is dependent on RIP1, -2, -3 and -4. Finally, we identified Lys51 and Lys145 of RIP4 as two critical residues for cIAP1-mediated ubiquitination and NF-κB activation.
publisher Public Library of Science
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171409/
_version_ 1611475169515143168

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