Source:http://linkedlifedata.com/resource/pubmed/id/11106668
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2001-5-25
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| pubmed:abstractText |
Although human c-IAP1 and c-IAP2 have been reported to possess antiapoptotic activity against a variety of stimuli in several mammalian cell types, we observed that full-length c-IAP1 and c-IAP2 failed to protect cells from apoptosis induced by Bax overexpression, tumor necrosis factor alpha treatment or Sindbis virus infection. However, deletion of the C-terminal RING domains of c-IAP1 and c-IAP2 restored antiapoptotic activity, indicating that this region negatively regulates the antiapoptotic function of the N-terminal BIR domain. This finding is consistent with the observation by others that the spacer region and RING domain of c-IAP1 functions as an E3 ligase, promoting autoubiquitination and degradation of c-IAP1. In addition, we found that c-IAP1 is cleaved during apoptosis to 52- and 35-kDa fragments. Both fragments contain the C-terminal end of c-IAP1 including the RING finger. In vitro cleavage of c-IAP1 with apoptotic cell extracts or with purified recombinant caspase-3 produced similar fragments. Furthermore, transfection of cells with the spacer-RING domain alone suppressed the antiapoptotic function of the N-terminal BIR domain of c-IAP1 and induced apoptosis. Optimal death-inducing activity of the spacer-RING required both the spacer region and the zinc-binding RING domain of c-IAP1 but did not require the caspase recruitment domain located within the spacer region. To the contrary, deletion of the caspase recruitment domain increased proapoptotic activity, apparently by stabilizing the C-terminal fragment.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc,
http://linkedlifedata.com/resource/pubmed/chemical/inhibitor of apoptosis...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
9
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| pubmed:volume |
276
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7602-8
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11106668-Animals,
pubmed-meshheading:11106668-Apoptosis,
pubmed-meshheading:11106668-Binding Sites,
pubmed-meshheading:11106668-CHO Cells,
pubmed-meshheading:11106668-Caspase 3,
pubmed-meshheading:11106668-Caspases,
pubmed-meshheading:11106668-Cell Line,
pubmed-meshheading:11106668-Cricetinae,
pubmed-meshheading:11106668-Gene Deletion,
pubmed-meshheading:11106668-Humans,
pubmed-meshheading:11106668-Immunoblotting,
pubmed-meshheading:11106668-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:11106668-Models, Genetic,
pubmed-meshheading:11106668-Mutagenesis, Site-Directed,
pubmed-meshheading:11106668-Plasmids,
pubmed-meshheading:11106668-Protein Binding,
pubmed-meshheading:11106668-Protein Structure, Tertiary,
pubmed-meshheading:11106668-Sindbis Virus,
pubmed-meshheading:11106668-Transfection,
pubmed-meshheading:11106668-Viral Proteins,
pubmed-meshheading:11106668-Zinc
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| pubmed:year |
2001
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| pubmed:articleTitle |
c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment.
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| pubmed:affiliation |
Department of Molecular Microbiology and Immunology, Johns Hopkins Schools of Public Health and Medicine, Baltimore, Maryland 21205, USA.
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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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