Linked Life Data

10446124

Source:http://linkedlifedata.com/resource/pubmed/id/10446124

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
1999-9-9
pubmed:abstractText
Upon activation of the Fas apoptotic signaling pathway, Bid, a "BH3 domain-only" pro-apoptotic molecule, is cleaved by caspase-8 into a 6.5-kDa N-terminal and a 15-kDa BH3 domain-containing C-terminal fragment, referred to as t(n)-Bid and t(c)-Bid, respectively. t(c)-Bid is a more potent inducer of apoptosis than full-length Bid, suggesting that the N-terminal region of Bid has an inhibitory effect on its pro-apoptotic activity. Here, we report the identification of a novel BH3-like motif (amino acid residues 35-43) in t(n)-Bid. Although Bid does not homodimerize, t(n)-Bid is able to associate avidly with t(c)-Bid. Site-directed mutagenesis revealed that both the novel BH3-like and BH3 domains are necessary for direct binding between t(n)-Bid and t(c)-Bid. While full-length Bid does not associate with t(n)-Bid, substitution of Leu(35), a critical residue in mediating t(n)-Bid/t(c)-Bid interaction, with Ala in full-length Bid is sufficient to establish Bid/t(n)-Bid interaction. Interestingly, the L35A Bid mutant is as effective as t(c)-Bid in inducing apoptosis and binding Bcl-X(L). We propose that the intramolecular interaction involving the BH3-like and BH3 domains serves to regulate the pro-apoptotic potential of Bid.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23687-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
A novel BH3-like domain in BID is required for intramolecular interaction and autoinhibition of pro-apoptotic activity.
pubmed:affiliation
Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Drive, Singapore 117609, Republic of Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't