DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ku, Bonsu | ko |
dc.contributor.author | Liang, Chengyu | ko |
dc.contributor.author | Jung, Jae U. | ko |
dc.contributor.author | Oh, Byung-Ha | ko |
dc.date.accessioned | 2013-03-09T16:58:49Z | - |
dc.date.available | 2013-03-09T16:58:49Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2011-04 | - |
dc.identifier.citation | CELL RESEARCH, v.21, no.4, pp.627 - 641 | - |
dc.identifier.issn | 1001-0602 | - |
dc.identifier.uri | http://hdl.handle.net/10203/96930 | - |
dc.description.abstract | Interactions between the BCL-2 family proteins determine the cell's fate to live or die. How they interact with each other to regulate apoptosis remains as an unsettled central issue. So far, the antiapoptotic BCL-2 proteins are thought to interact with BAX weakly, but the physiological significance of this interaction has been vague. Herein, we show that recombinant BCL-2 and BCL-w interact potently with a BCL-2 homology (BH) 3 domain-containing peptide derived from BAX, exhibiting the dissociation constants of 15 and 23 nM, respectively. To clarify the basis for this strong interaction, we determined the three-dimensional structure of a complex of BCL-2 with a BAX peptide spanning its BH3 domain. It revealed that their interactions extended beyond the canonical BH3 domain and involved three nonconserved charged residues of BAX. A novel BAX variant, containing the alanine substitution of these three residues, had greatly impaired affinity for BCL-2 and BCL-w, but was otherwise indistinguishable from wild-type BAX. Critically, the apoptotic activity of the BAX variant could not be restrained by BCL-2 and BCL-w, pointing that the observed tight interactions are critical for regulating BAX activation. We also comprehensively quantified the binding affinities between the three BCL-2 subfamily proteins. Collectively, the data show that due to the high affinity of BAX for BCL-2, BCL-w and A1, and of BAK for BCL-XL, MCL-1 and A1, only a subset of BH3-only proteins, commonly including BIM, BID and PUMA, could be expected to free BAX or BAK from the antiapoptotic BCL-2 proteins to elicit apoptosis. | - |
dc.language | English | - |
dc.publisher | INST BIOCHEMISTRY & CELL BIOLOGY | - |
dc.subject | CELL-DEATH | - |
dc.subject | MITOCHONDRIAL APOPTOSIS | - |
dc.subject | BH3-ONLY PROTEINS | - |
dc.subject | FAMILY | - |
dc.subject | BINDING | - |
dc.subject | MCL-1 | - |
dc.subject | PERMEABILIZATION | - |
dc.subject | MEMBRANE | - |
dc.subject | DISTINCT | - |
dc.subject | COMPLEX | - |
dc.title | Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX | - |
dc.type | Article | - |
dc.identifier.wosid | 000289230800009 | - |
dc.identifier.scopusid | 2-s2.0-79954419930 | - |
dc.type.rims | ART | - |
dc.citation.volume | 21 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 627 | - |
dc.citation.endingpage | 641 | - |
dc.citation.publicationname | CELL RESEARCH | - |
dc.identifier.doi | 10.1038/cr.2010.149 | - |
dc.contributor.localauthor | Oh, Byung-Ha | - |
dc.contributor.nonIdAuthor | Ku, Bonsu | - |
dc.contributor.nonIdAuthor | Liang, Chengyu | - |
dc.contributor.nonIdAuthor | Jung, Jae U. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | BAX | - |
dc.subject.keywordAuthor | BCL-2 | - |
dc.subject.keywordAuthor | BCL-w | - |
dc.subject.keywordAuthor | structure | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | MITOCHONDRIAL APOPTOSIS | - |
dc.subject.keywordPlus | BH3-ONLY PROTEINS | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | MCL-1 | - |
dc.subject.keywordPlus | PERMEABILIZATION | - |
dc.subject.keywordPlus | MEMBRANE | - |
dc.subject.keywordPlus | DISTINCT | - |
dc.subject.keywordPlus | COMPLEX | - |
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