BH3-interacting domain death agonist (BID) (BID)

BH3-interacting domain death agonist (BID) is a pro-apoptotic member of the Bcl-2 protein family that serves as a critical bridge between the extrinsic and intrinsic apoptotic pathways (UniProt: P55957). In its inactive form, BID resides in the cytosol; however, upon cleavage by caspase-8 or other proteases, it is converted into its active truncated form, tBID, which translocates to the mitochondria (PubMed: 14585919). Once at the mitochondria, tBID facilitates mitochondrial outer membrane permeabilization (MOMP) by activating the pore-forming proteins BAX and BAK, leading to the release of cytochrome c and subsequent cell death (PubMed: 11062262). Dysregulation of BID is frequently observed in various cancers, where its downregulation or inhibition contributes to resistance against chemotherapy and death receptor-mediated apoptosis (PubMed: 15660110). Conversely, overactivation of BID has been implicated in pathological cell death seen in neurodegenerative disorders and organ injury, such as ischemic stroke (PubMed: 11553315). While BID itself is a challenging direct therapeutic target, its pathway is modulated by experimental small molecules like BI-11C7 and is a key component of the response to TRAIL-based therapies (PubMed: 21832056).

Other names

BH3-interacting domain death agonistp22 BIDtBIDtruncated BIDHuman BIDFP497

BID acts as a molecular switch that connects the extrinsic apoptotic pathway to the intrinsic mitochondrial pathway. Therapeutic strategies involve either inhibiting BID cleavage/translocation to prevent pathological cell death (e.g., in stroke or liver injury) or utilizing its pathway via death receptor agonists (e.g., TRAIL) to induce apoptosis in cancer cells (PubMed: 21832056, PubMed: 11553315).