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rdf:type |
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lifeskim:mentions |
umls-concept:C0033414,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0599697,
umls-concept:C0758915,
umls-concept:C0910167,
umls-concept:C1180347,
umls-concept:C1337108,
umls-concept:C1705156,
umls-concept:C1706853,
umls-concept:C1879748,
umls-concept:C2700400
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pubmed:issue |
2
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pubmed:dateCreated |
2001-3-27
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pubmed:abstractText |
The Tpl-2 proto-oncoprotein promotes cellular proliferation when overexpressed in a variety of tumor cell lines. Here, we present evidence that when overexpressed in immortalized non-transformed cells, Tpl-2 induces apoptosis by promoting the activation of caspase-3 via a caspase-9-dependent mechanism, and that apoptosis is enhanced when Tpl-2 is co-expressed with the newly identified ankyrin repeat protein Tvl-1. The activation of caspase-3 by caspase-9 is known to depend on the assembly of a multimolecular complex that includes Apaf-1 and caspase-9. Data presented here show that co-expression of Tpl-2 with Tvl-1 promotes the assembly of a complex that involves several proteins that bind Apaf-1 including Tvl-1, itself, Tpl-2 and phosphorylated procaspase-9. More important, procaspase-3, which under normal growth conditions is not associated with the complex, binds Tvl-1 conditionally in response to Tpl-2-generated apoptotic signals. The conditional association of procaspase-3 with Tvl-1 promotes the in vivo proteolytic maturation of procaspase-3 by caspase-9, a process casually linked to apoptosis.
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pubmed:grant |
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/APAF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Apaf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Apaf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptotic Protease-Activating...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP3K8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k8 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Map3k8 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rfxank protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9541
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
187
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
176-87
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:11267997-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11267997-Amino Acid Sequence,
pubmed-meshheading:11267997-Animals,
pubmed-meshheading:11267997-Apoptosis,
pubmed-meshheading:11267997-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:11267997-Carrier Proteins,
pubmed-meshheading:11267997-Caspase 3,
pubmed-meshheading:11267997-Caspase 9,
pubmed-meshheading:11267997-Caspases,
pubmed-meshheading:11267997-Cell Line,
pubmed-meshheading:11267997-Enzyme Activation,
pubmed-meshheading:11267997-Enzyme Precursors,
pubmed-meshheading:11267997-Fibroblasts,
pubmed-meshheading:11267997-Gene Expression,
pubmed-meshheading:11267997-Humans,
pubmed-meshheading:11267997-Kidney,
pubmed-meshheading:11267997-MAP Kinase Kinase Kinases,
pubmed-meshheading:11267997-Molecular Sequence Data,
pubmed-meshheading:11267997-Phosphorylation,
pubmed-meshheading:11267997-Protein Binding,
pubmed-meshheading:11267997-Proteins,
pubmed-meshheading:11267997-Proto-Oncogene Proteins,
pubmed-meshheading:11267997-Rats
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pubmed:year |
2001
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pubmed:articleTitle |
Tpl-2 induces apoptosis by promoting the assembly of protein complexes that contain caspase-9, the adapter protein Tvl-1, and procaspase-3.
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pubmed:affiliation |
Fox Chase Cancer Center, Philadelphia, Pensylvania, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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