Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-11-17
pubmed:abstractText
While activation of BAX/BAK by BH3-only molecules (BH3s) is essential for mitochondrial apoptosis, the underlying mechanisms remain unsettled. Here we demonstrate that BAX undergoes stepwise structural reorganization leading to mitochondrial targeting and homo-oligomerization. The alpha1 helix of BAX keeps the alpha9 helix engaged in the dimerization pocket, rendering BAX as a monomer in cytosol. The activator BH3s, tBID/BIM/PUMA, attack and expose the alpha1 helix of BAX, resulting in secondary disengagement of the alpha9 helix and thereby mitochondrial insertion. Activator BH3s remain associated with the N-terminally exposed BAX through the BH1 domain to drive homo-oligomerization. BAK, an integral mitochondrial membrane protein, has bypassed the first activation step, explaining why its killing kinetics are faster than those of BAX. Furthermore, death signals initiated at ER induce BIM and PUMA to activate mitochondrial apoptosis. Accordingly, deficiency of Bim/Puma impedes ER stress-induced BAX/BAK activation and apoptosis. Our study provides mechanistic insights regarding the spatiotemporal execution of BAX/BAK-governed cell death.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-10085289, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-10085290, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-10228148, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-10934477, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-10950869, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11106734, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11163212, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11175253, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11326099, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11462023, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11583631, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-11711427, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12209154, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12242151, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12419244, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12510191, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12529375, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12624178, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12732850, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12847083, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-12881569, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-14744432, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-15037603, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-15574335, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-15613488, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-15721256, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-16697956, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-16729025, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-16763614, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17052454, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17115033, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17289999, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17453159, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17604722, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-17671092, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-18097445, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-18314333, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-18426910, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-18471982, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-18948948, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-19062087, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-19244344, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-19917244, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-8521816, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-8861942, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-8918887, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9020082, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9153240, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9363757, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9382873, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9742125, http://linkedlifedata.com/resource/pubmed/commentcorrection/19917256-9763432
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death..., http://linkedlifedata.com/resource/pubmed/chemical/Bak1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bcl-2-like protein 11, http://linkedlifedata.com/resource/pubmed/chemical/Etoposide, http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PUMA protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer..., http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1097-4164
pubmed:author
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