BID

BID Background

The BID gene encodes the BH3-interacting domain death agonist (BID), a pro-apoptotic member of the Bcl-2 protein family ^[1]. BID possesses a single BH3 (Bcl-2 homology 3) domain and lacks a C-terminal transmembrane domain for the outer mitochondrial membrane[1]. BID is localized in the cytosolic or on the plasma membrane. BID is inactive, but becomes activated after Caspase-8 cleavage ^[2][3][4]. Truncated BID (tBID) may expose the BH3 motif buried in the uncleaved molecule. Protease-cleaved BID subsequently translocates to mitochondria where it induces permeabilization of the mitochondrial outer membrane (MOM) dependent on the pro-apoptotic proteins Bax and/or Bak. BID, therefore, acts as a sentinel for protease-mediated death signals ^[7]. Mutagenesis study indicated that the BH3 domain is required for the apoptotic activity of BID since BID with an intact BH3 domain may retain interaction with BAX ^[4][5]. Cells generate pro-apoptotic proteins with a single active domain called BH3 in stress or damage. BID acts as an activator to induce the overexpression of effector pro-apoptotic proteins such as BAX (BCL2-associated X) and BAK (BCL2 antagonist/killer 1) ^[6]. The production of BAX and BAK further leads to cytochrome c release into the cytoplasm, following caspase activation and apoptosis ^[6].

[1] Wang K, Yin XM, et al. BID: a novel BH3 domain-only death agonist [J]. Genes Dev. 1996, 10 (22): 2859-9.
[2] Gross A., Yin X.-M., et al. Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not TNF-R1/Fas death [J]. J. Biol. Chem. 1999; 274: 1156-1163.
[3] Li H., Zhu H., et al. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis [J]. Cell. 1998; 94: 491-501.
[4] Luo X., Budihardjo I. et al. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors [J]. Cell. 1998; 94: 481-490.
[5] Wang K., Gross A., et al. Mutagenesis of the BH3 domain of BAX identifies residues critical for dimerization and killing [J]. Mol. Cell. Biol. 1998; 18: 6083-6089.
[6] Korsmeyer SJ, Wei MC, et al. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c [J]. Cell Death Differ 2001; 7: 1166-173.