Scientific Background | BID differs from BAK and BAX in category, not just sequence. It is a BH3-only protein, meaning it carries the BH3 motif without the other domains of the family, and it functions as an activator: rather than being an effector of membrane permeabilisation, it triggers the effectors. It was described as a novel BH3 domain-only death agonist when first characterised. Its place in the pathway is what gives it distinctive experimental value. BID is cleaved by caspase-8 downstream of death receptor signalling, and the truncated product tBID moves to the mitochondrial outer membrane, where it engages BAK and BAX. This is the principal route by which an extrinsic death signal is amplified through the mitochondria, and stepwise activation of BAX and BAK by tBID, BIM and PUMA has been characterised in detail. The BID BH3 domain is the part of the protein that carries out that engagement. Because BID activates effectors directly rather than only occupying anti-apoptotic proteins, a BID BH3 peptide behaves as a so-called activator BH3 peptide in profiling experiments, and it is grouped with BIM rather than with sensitiser peptides such as BAD or NOXA. This product supplies the core BH3 segment; the longer N-terminally extended version is offered separately as LT1054, and cell-permeable polyarginine conjugates as LT1052 and LT1053. |
References | 1. Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ. BID: a novel BH3 domain-only death agonist. Genes & Development (1996) 10:2859. Genes Dev 1996;10:2859 2. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. PMC3163439 3. Wei MC, et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes & Development (2000) 14:2060. Genes Dev 2000;14:2060 |
