Linked Life Data

18195012

Source:http://linkedlifedata.com/resource/pubmed/id/18195012

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-3-17
pubmed:abstractText
BIM and tBID are two BCL-2 homology 3 (BH3)-only proteins with a particularly strong capacity to trigger BAX-driven mitochondrial outer membrane permeabilization, a crucial event in mammalian apoptosis. However, the means whereby BIM and tBID fulfill this task is controversial. Here, we used a reconstituted liposomal system bearing physiological relevance to explore systematically how the BAX-permeabilizing function is influenced by interactions of BIM/BID-derived proteins and BH3 motifs with multidomain BCL-2 family members and with membrane lipids. We found that nanomolar dosing of BIM proteins sufficed to reverse completely the inhibition of BAX permeabilizing activity exerted by all antiapoptotic proteins tested (BCL-2, BCL-X(L), BCL-W, MCL-1, and A1). This effect was reproducible by a peptide representing the BH3 motif of BIM, whereas an equivalent BID BH3 peptide was less potent and more selective, reversing antiapoptotic inhibition. On the other hand, in the absence of BCL-2-type proteins, BIM proteins and the BIM BH3 peptide were inefficient, directly triggering the BAX-permeabilizing function. In contrast, tBID alone potently assisted BAX to permeabilize membranes at least in part by producing a structural distortion in the lipid bilayer via BH3-independent interaction of tBID with cardiolipin. Together, these results support the notion that BIM and tBID follow different strategies to trigger BAX-driven mitochondrial outer membrane permeabilization with strong potency.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7790-803
pubmed:meshHeading
pubmed-meshheading:18195012-Amino Acid Motifs, pubmed-meshheading:18195012-Animals, pubmed-meshheading:18195012-Apoptosis Regulatory Proteins, pubmed-meshheading:18195012-BH3 Interacting Domain Death Agonist Protein, pubmed-meshheading:18195012-Cardiolipins, pubmed-meshheading:18195012-Cell Membrane Permeability, pubmed-meshheading:18195012-Humans, pubmed-meshheading:18195012-Liposomes, pubmed-meshheading:18195012-Male, pubmed-meshheading:18195012-Membrane Proteins, pubmed-meshheading:18195012-Mitochondria, Liver, pubmed-meshheading:18195012-Peptides, pubmed-meshheading:18195012-Protein Binding, pubmed-meshheading:18195012-Protein Structure, Tertiary, pubmed-meshheading:18195012-Proto-Oncogene Proteins, pubmed-meshheading:18195012-Rats, pubmed-meshheading:18195012-Rats, Sprague-Dawley, pubmed-meshheading:18195012-bcl-2-Associated X Protein
pubmed:year
2008
pubmed:articleTitle
BIM and tBID are not mechanistically equivalent when assisting BAX to permeabilize bilayer membranes.
pubmed:affiliation
Unidad de Biofísica (Centro Mixto Consejo Superior de Investigaciones Cientificas, Universidad del Pais Vasco/Euskal Herriko Unibertsitatea), Universidad del Pais Vasco/Euskal Herriko Unibertsitatea, 48080 Bilbao, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't