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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 3
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pubmed:dateCreated |
2004-3-8
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pubmed:abstractText |
Ubiquitination regulates the stability and/or activity of numerous cellular proteins. The corollary is that de-ubiquitinating enzymes, which 'trim' polyubiquitin chains from specific substrate proteins, play key roles in controlling fundamental cellular activities. Ubiquitin is essential at several stages during the activation of NF-kappaB (nuclear factor kappaB), a central co-ordinator of inflammation and other immune processes. Ubiquitination is known to cause degradation of the inhibitory molecule IkappaBalpha (inhibitor of kappaB). In addition, activation of TRAF (tumour-necrosis-factor-receptor-associated factor) and IKKgamma (IkappaB kinase gamma)/NEMO (NF-kappaB essential modifier) signal adaptors relies on their modification with 'nonclassical' forms of polyubiquitin chains. Ubiquitin also plays a key role in determining cell fate by modulating the stability of numerous pro-apoptotic or anti-apoptotic proteins. The zinc-finger protein A20 has dual functions in inhibiting NF-kappaB activation and suppressing apoptosis. The molecular mechanisms of these anti-inflammatory and cytoprotective effects are unknown. Here we demonstrate that A20 is a de-ubiquitinating enzyme. It contains an N-terminal catalytic domain that belongs to the ovarian-tumour superfamily of cysteine proteases. A20 cleaved ubiquitin monomers from branched polyubiquitin chains linked through Lys48 or Lys63 and bound covalently to a thiol-group-reactive, ubiquitin-derived probe. Mutation of a conserved cysteine residue in the catalytic site (Cys103) abolished these activities. A20 did not have a global effect on ubiquitinated cellular proteins, which indicates that its activity is target-specific. The biological significance of the catalytic domain is unknown.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10435631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10471497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10664582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10755617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10835629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-10837071,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11009421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11057907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11435423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11463333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11566882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11583613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11594795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11825870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-11923872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12183636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12401499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12507430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12591926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12682062,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12704427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12753742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12867425,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12917689,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12917690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-12917691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-1381359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-7539000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-7578059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-8692885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-8797804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14748687-8970991
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
378
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
727-34
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14748687-Animals,
pubmed-meshheading:14748687-Catalytic Domain,
pubmed-meshheading:14748687-Cell Line,
pubmed-meshheading:14748687-Cell Survival,
pubmed-meshheading:14748687-Endopeptidases,
pubmed-meshheading:14748687-Humans,
pubmed-meshheading:14748687-Hydrolysis,
pubmed-meshheading:14748687-Inflammation,
pubmed-meshheading:14748687-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:14748687-Nuclear Proteins,
pubmed-meshheading:14748687-Polyubiquitin,
pubmed-meshheading:14748687-Proteins,
pubmed-meshheading:14748687-Ubiquitins,
pubmed-meshheading:14748687-Zinc Fingers
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pubmed:year |
2004
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pubmed:articleTitle |
Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity.
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pubmed:affiliation |
Molecular Immunology Programme, The Babraham Institute, Cambridge CB2 4AT, UK. paul.evans@bbsrc.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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