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

Description of BID Protein / BH3-interacting domain death agonist(BID)

General information on BID protein

BID protein stands for BH3 interacting-domain death antagonist. It is a pro-apoptotic member of BCL2 family of proteins. The members of the BC-2 family share at least one of the four BCL-2 homology (BH) domains also known as BH1, BH2, BH3 and B4. Based on this, members of this family of proteins can form hetero- or homodimers. Bcl-2 family of proteins are involved in a variety of cellular activities and, depending on the protein, can act as pro-apoptotic or pro-apoptotic regulators.
nnBID protein interacts with different proteins such as ATR/ATRIP, BCL2, CASP2, CASP8, MCL1 , RPA and Bax. In response to apoptotic signal, BID protein interacts with Bax which allows the insertion of Bax primarly in the outer membrane of mitochondria. It is believed that this leads to the opening voltage-dependent anion channel (VDAC) of the mitochondria. This induces the release of cytochrome c and other pro-apoptotic factors from mitochondria. This results in the activation of caspases which are a family of protease enzymes that regulate programmed cell death. The ability of BID protein to bind to Bax protein is inhibited by ant-apoptotic Bcl-2 proteins including BCl-2 protein. The latter sequesters BID proteins which results in reduced Bax protein activation.
nThe expression of BID protein are regulated by p53 tumor suppressor. The latter is a transcription factor and has been linked to the regulation of cell cycle, cell apoptosis and genomic stability. P53 is activated as a result of cell’s response to stress which induces many downstream targets including BID protein. Other apoptotic stimuli include N-hydroxy-L-arginine (NOHA), an intermediate product formed as a result of L-arginine converting to nitric oxide. The latter activates caspase 8 which in turn activates its substrate BID protein. The BID cleavage induces cytochrome-c mediated apoptosis. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has also been linked to the activation of caspase-8 and BID cleavage by activating caspase-9 via cytochrome-c.