Source:http://linkedlifedata.com/resource/pubmed/id/11410287
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-6-18
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pubmed:abstractText |
Through interaction with a multitude of target proteins, 14-3-3 proteins participate in the regulation of diverse cellular processes including apoptosis. These 14-3-3-interacting proteins include a proapoptotic Bcl-2 homolog, Bad (Bcl-2/Bcl-XL-associated death promoter). To understand how 14-3-3 interacts with Bad and modulates its function, we have identified structural elements of 14-3-3 necessary for 14-3-3/Bad association. 14-3-3 contains a conserved amphipathic groove that is required for binding to several of its ligands. We used peptides of known binding specificity as competitors to demonstrate that Bad interacts with 14-3-3zeta via its amphipathic groove. More detailed analysis revealed that several conserved residues in the groove, including Lys-49, Val-176, and Leu-220, were critical for Bad interaction. These results were applied to investigations of the ability of 14-3-3 to prevent Bad-induced cell death. When co-expressed with Akt, wild-type 14-3-3 could reduce the ability of Bad to cause death, however 14-3-3zetaK49E, which cannot bind Bad, failed to inhibit Bad. It seems that the amphipathic groove of 14-3-3 represents a general binding site for multiple ligands, raising issues related to competition of ligands for 14-3-3.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BAD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-3002
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
1547
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
313-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11410287-14-3-3 Proteins,
pubmed-meshheading:11410287-Apoptosis,
pubmed-meshheading:11410287-Binding, Competitive,
pubmed-meshheading:11410287-Binding Sites,
pubmed-meshheading:11410287-Carrier Proteins,
pubmed-meshheading:11410287-Cell Line,
pubmed-meshheading:11410287-Humans,
pubmed-meshheading:11410287-Mutation,
pubmed-meshheading:11410287-Phosphopeptides,
pubmed-meshheading:11410287-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11410287-Signal Transduction,
pubmed-meshheading:11410287-Tyrosine 3-Monooxygenase,
pubmed-meshheading:11410287-bcl-Associated Death Protein,
pubmed-meshheading:11410287-bcl-X Protein
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pubmed:year |
2001
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pubmed:articleTitle |
The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta.
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pubmed:affiliation |
Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, GA 30322, 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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