18178551

Source:http://linkedlifedata.com/resource/pubmed/id/18178551

Download in:

Switch to

Custom View

Named Graph Language Inference

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0015744, umls-concept:C0037083, umls-concept:C0079904, umls-concept:C0205160, umls-concept:C0205314, umls-concept:C0301625, umls-concept:C0679622, umls-concept:C1333282, umls-concept:C1710082, umls-concept:C2911691
pubmed:issue	11
pubmed:dateCreated	2008-3-10
pubmed:abstractText	Transcription factors belonging to the NF-kappaB family regulate inflammation by inducing pro-inflammatory molecules (e.g. interleukin (IL)-8) in response to cytokines (e.g. tumor necrosis factor (TNF) alpha, IL-1) or other stimuli. Several negative regulators of NF-kappaB, including the ubiquitin-editing enzyme A20, participate in the resolution of inflammatory responses. We report that Cezanne, a member of the A20 family of the deubiquitinating cysteine proteases, can be induced by TNFalpha in cultured cells. Silencing of endogenous Cezanne using small interfering RNA led to elevated NF-kappaB luciferase reporter gene activity and enhanced expression of IL-8 transcripts in TNFalpha-treated cells. Thus we conclude that endogenous Cezanne can attenuate NF-kappaB activation and the induction of pro-inflammatory transcripts in response to TNF receptor (TNFR) signaling. Overexpression studies revealed that Cezanne suppressed NF-kappaB nuclear translocation and transcriptional activity by targeting the TNFR signaling pathway at the level of the IkappaB kinase complex or upstream from it. These effects were not observed in a form of Cezanne that was mutated at the catalytic cysteine residue (Cys209), indicating that the deubiquitinating activity of Cezanne is essential for NF-kappaB regulation. Finally, we demonstrate that Cezanne can be recruited to activated TNFRs where it suppresses the build-up of polyubiquitinated RIP1 signal adapter proteins. Thus we conclude that Cezanne forms a novel negative feedback loop in pro-inflammatory signaling and that it suppresses NF-kappaB activation by targeting RIP1 signaling intermediaries for deubiquitination.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/2985121R
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/AGFG1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Lysine, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Pore Complex Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/OTUD7B protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor, http://linkedlifedata.com/resource/pubmed/chemical/TNFAIP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
pubmed:status	MEDLINE
pubmed:month	Mar
pubmed:issn	0021-9258
pubmed:author	pubmed-author:ChaudhuryHeraH, pubmed-author:DeanJonathan L EJL, pubmed-author:EnesaKarineK, pubmed-author:EvansPaul CPC, pubmed-author:HaskardDorian ODO, pubmed-author:LuongLe Ale A, pubmed-author:MasonJustin CJC, pubmed-author:RawlinsonLesleyL, pubmed-author:ZakkarMustafaM
pubmed:issnType	Print
pubmed:day	14
pubmed:volume	283
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	7036-45
pubmed:dateRevised	2010-9-20
pubmed:meshHeading	pubmed-meshheading:18178551-Endopeptidases, pubmed-meshheading:18178551-Endothelial Cells, pubmed-meshheading:18178551-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18178551-Humans, pubmed-meshheading:18178551-Inflammation, pubmed-meshheading:18178551-Interleukin-8, pubmed-meshheading:18178551-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:18178551-Lysine, pubmed-meshheading:18178551-Models, Biological, pubmed-meshheading:18178551-Mutation, pubmed-meshheading:18178551-NF-kappa B, pubmed-meshheading:18178551-Nuclear Pore Complex Proteins, pubmed-meshheading:18178551-Nuclear Proteins, pubmed-meshheading:18178551-RNA-Binding Proteins, pubmed-meshheading:18178551-Receptors, Tumor Necrosis Factor, pubmed-meshheading:18178551-Signal Transduction, pubmed-meshheading:18178551-Ubiquitin
pubmed:year	2008
pubmed:articleTitle	NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling.
pubmed:affiliation	British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London W12 ONN, United Kingdom.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't