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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2005-8-11
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pubmed:abstractText |
Bfl-1/A1 is generally recognized as a Bcl-2-related inhibitor of apoptosis. We show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover. Moreover, while Bfl-1 suppresses apoptosis induced by staurosporine or cytokine withdrawal, it is proapoptotic in response to tumor necrosis factor (TNF) receptor activation in FL5.12 pro-B cells. Its anti- versus proapoptotic effect is regulated by two proteolytic events: (1) its constitutive proteasome-mediated turnover and (2) its TNF/cycloheximide (CHX)-induced cleavage by mu-calpain, or a calpain-like activity, coincident with acquisition of a proapoptotic phenotype. In vitro studies suggest that calpain-mediated cleavage of Bfl-1 occurs between its Bcl-2 homology (BH)4 and BH3 domains. This would be consistent with the generation of a proapoptotic Bax-like BH1-3 molecule. Overall, our studies uncovered two new regulatory mechanisms that play a decisive role in determining Bfl-1's prosurvival versus prodeath activities. These findings might provide important clues to counteract chemoresistance in tumor cells that highly express Bfl-1.
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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/BCL2-related protein A1,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/mu-calpain
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1225-39
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16094403-Amino Acid Sequence,
pubmed-meshheading:16094403-Animals,
pubmed-meshheading:16094403-Apoptosis,
pubmed-meshheading:16094403-B-Lymphocytes,
pubmed-meshheading:16094403-Calpain,
pubmed-meshheading:16094403-Cell Death,
pubmed-meshheading:16094403-Cell Line,
pubmed-meshheading:16094403-Cycloheximide,
pubmed-meshheading:16094403-Flow Cytometry,
pubmed-meshheading:16094403-Green Fluorescent Proteins,
pubmed-meshheading:16094403-Humans,
pubmed-meshheading:16094403-Immunoprecipitation,
pubmed-meshheading:16094403-Lysine,
pubmed-meshheading:16094403-Mice,
pubmed-meshheading:16094403-Models, Biological,
pubmed-meshheading:16094403-Molecular Sequence Data,
pubmed-meshheading:16094403-Mutagenesis,
pubmed-meshheading:16094403-Mutation,
pubmed-meshheading:16094403-Phenotype,
pubmed-meshheading:16094403-Plasmids,
pubmed-meshheading:16094403-Proteasome Endopeptidase Complex,
pubmed-meshheading:16094403-Protein Binding,
pubmed-meshheading:16094403-Protein Biosynthesis,
pubmed-meshheading:16094403-Protein Structure, Tertiary,
pubmed-meshheading:16094403-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:16094403-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:16094403-Sequence Homology, Amino Acid,
pubmed-meshheading:16094403-Staurosporine,
pubmed-meshheading:16094403-Transfection,
pubmed-meshheading:16094403-Ubiquitin
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pubmed:year |
2005
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pubmed:articleTitle |
Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a prodeath factor.
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pubmed:affiliation |
Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5638, 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,
Research Support, N.I.H., Extramural
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