Title |
cIAP1/2 Are Direct E3 Ligases Conjugating Diverse Types of Ubiquitin Chains to Receptor Interacting Proteins Kinases 1 to 4 (RIP1–4)
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Published in |
PLOS ONE, September 2011
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DOI | 10.1371/journal.pone.0022356 |
Pubmed ID | |
Authors |
Mathieu J. M. Bertrand, Saskia Lippens, An Staes, Barbara Gilbert, Ria Roelandt, Jelle De Medts, Kris Gevaert, Wim Declercq, Peter Vandenabeele |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 2% |
United States | 2 | 2% |
Canada | 2 | 2% |
Sweden | 1 | <1% |
Netherlands | 1 | <1% |
Korea, Republic of | 1 | <1% |
Unknown | 108 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 28 | 24% |
Student > Ph. D. Student | 27 | 23% |
Student > Bachelor | 13 | 11% |
Student > Master | 11 | 9% |
Other | 8 | 7% |
Other | 17 | 15% |
Unknown | 13 | 11% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 45 | 38% |
Biochemistry, Genetics and Molecular Biology | 32 | 27% |
Medicine and Dentistry | 10 | 9% |
Immunology and Microbiology | 7 | 6% |
Chemistry | 4 | 3% |
Other | 8 | 7% |
Unknown | 11 | 9% |