Please use this identifier to cite or link to this item:
|Title:||A novel BH3-like domain in BID is required for intramolecular interaction and autoinhibition of pro-apoptotic activity|
|Citation:||Tan, K.O., Tan, K.M.L., Yu, V.C. (1999-08-20). A novel BH3-like domain in BID is required for intramolecular interaction and autoinhibition of pro-apoptotic activity. Journal of Biological Chemistry 274 (34) : 23687-23690. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.274.34.23687|
|Abstract:||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(c)-Bid. Although Bid does not homodimerize, t(c)-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(n)-Bid. While full-length Bid does not associate with t(n)-Bid, substitution of Leu35, 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.|
|Source Title:||Journal of Biological Chemistry|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Dec 6, 2018
WEB OF SCIENCETM
checked on Nov 28, 2018
checked on Dec 7, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.