BH3 interacting-domain death agonist

The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family.[5] Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

BID
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZY3, 2BID, 2KBW, 2M5B, 2M5I, 4BD2, 4ZEQ, 5AJJ, 4QVE, 4ZIG, 4ZII, 5C3F
Identifiers
Aliases	BID, Bid, 2700049M22Rik, AI875481, AU022477, FP497, BH3 interacting domain death agonist
External IDs	OMIM: 601997 MGI: 108093 HomoloGene: 923 GeneCards: BID
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q11.21 Start 17,734,138 bp[1] End 17,774,770 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F1|6 57.02 cM Start 120,891,930 bp[2] End 120,916,853 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • death receptor binding • GO:0001948 protein binding • ubiquitin protein ligase binding • protein heterodimerization activity Cellular component • cytoplasm • membrane • mitochondrial membranes • mitochondrial outer membrane • mitochondrion • integral component of mitochondrial membrane • cytosol Biological process • neuron apoptotic process • positive regulation of protein homooligomerization • positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway • extrinsic apoptotic signaling pathway • signal transduction in response to DNA damage • regulation of protein oligomerization • establishment of protein localization to membrane • protein targeting to mitochondrion • regulation of mitochondrial membrane permeability involved in apoptotic process • regulation of G1/S transition of mitotic cell cycle • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • regulation of cell proliferation • apoptotic mitochondrial changes • positive regulation of protein oligomerization • positive regulation of apoptotic process • positive regulation of release of cytochrome c from mitochondria • positive regulation of extrinsic apoptotic signaling pathway • protein homooligomerization • activation of cysteine-type endopeptidase activity involved in apoptotic process • mitochondrial outer membrane permeabilization • extrinsic apoptotic signaling pathway via death domain receptors • hepatocyte apoptotic process • release of cytochrome c from mitochondria • apoptotic process • regulation of apoptotic process • positive regulation of mitochondrial membrane potential • mitochondrial ATP synthesis coupled electron transport • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage • positive regulation of fibroblast apoptotic process • positive regulation of apoptotic signaling pathway • negative regulation of apoptotic process • positive regulation of intrinsic apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	637	12122
Ensembl	ENSG00000015475	ENSMUSG00000004446
UniProt	P55957	P70444
RefSeq (mRNA)	NM_001196 NM_001244567 NM_001244569 NM_001244570 NM_001244572 NM_197966 NM_197967	NM_007544
RefSeq (protein)	NP_001187 NP_001231496 NP_001231498 NP_001231499 NP_001231501 NP_932070 NP_932071 NP_001187.1 NP_001231496.1	NP_031570
Location (UCSC)	Chr 22: 17.73 – 17.77 Mb	Chr 6: 120.89 – 120.92 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

BID
human pro-apoptotic protein bid
Identifiers
Symbol	BID
Pfam	PF06393
InterPro	IPR010479
SCOPe	1ddb / SUPFAM
TCDB	1.A.21
OPM superfamily	40
OPM protein	2m5i
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Interactions

BID is a pro-apoptotic Bcl-2 protein containing only the BH3 domain. In response to apoptotic signaling, BID interacts with another Bcl-2 family protein, Bax, leading to the insertion of Bax into organelle membranes, primarily the outer mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This results in the release of cytochrome c and other pro-apoptotic factors (such as SMAC/DIABLO)[6] from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of caspases. This defines BID as a direct activator of Bax, a role common to some of the pro-apoptotic Bcl-2 proteins containing only the BH3 domain.

The anti-apoptotic Bcl-2 proteins, including Bcl-2 itself, can bind BID and inhibit BID's ability to activate Bax. As a result, the anti-apoptotic Bcl-2 proteins may inhibit apoptosis by sequestering BID, leading to reduced Bax activation.

The expression of BID is upregulated by the tumor suppressor p53, and BID has been shown to be involved in p53-mediated apoptosis.[7] The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BID. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting Bax activation and the insertion of Bax into the mitochondrial membrane.

The BH3 interacting-domain death agonist has been shown to interact with:

• ATR/ATRIP,[8]
• BCL2,[9][10]
• CASP2,[11][12]
• CASP8,[11][13]
• MCL1,[9][14] and
• RPA.[15]

Cleavage

Caspase-8 (as surface) cleavage of Bid (as ribbon) (visualization by Kosi Gramatikoff)

Several reports have demonstrated that caspase-8, and its substrate BID, are frequently activated in response to certain apoptotic stimuli in a death receptor-independent manner. N-hydroxy-L-arginine (NOHA), a stable intermediate product formed during the conversion of L-arginine to nitric oxide activates caspase-8.[16] Activation of caspase-8, and subsequent BID cleavage participate in cytochrome-c mediated apoptosis.[17] 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mediated activation of caspase-9 via cytochrome-c release has been shown to result in the activation of caspase-8 and Bid cleavage.[18] Aspirin and Curcumin (diferuloylmethane) too activate caspase-8 to cleave and translocate Bid, induced a conformational change in and translocation of Bax and cytochrome-c release.[19][20]

See also

• Apoptosis
• Apoptosome
• Bcl-2
• Bcl-2-associated X protein (BAX)
• Caspases
• Cytochrome c
• Noxa
• Mitochondrion
• p53 upregulated modulator of apoptosis (PUMA)

References

1. GRCh38: Ensembl release 89: ENSG00000015475 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004446 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wang K, Yin XM, Chao DT, Milliman CL, Korsmeyer SJ (1996). "BID: a novel BH3 domain-only death agonist". Genes Dev. 10 (22): 2859–69. doi:10.1101/gad.10.22.2859. PMID 8918887.
6. Weinberg, Robert A. (2007). The biology of cancer. New York: Taylor & Francis. p. 341. ISBN 978-0-8153-4076-8.
7. Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS (2002). "BID regulation by p53 contributes to chemosensitivity". Nat. Cell Biol. 4 (11): 842–9. doi:10.1038/ncb866. PMID 12402042.
8. Liu Y, Bertram CC, Shi Q, Zinkel SS (2011). "Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress". Cell Death Differ. 18 (5): 841–52. doi:10.1038/cdd.2010.151. PMC 3074003. PMID 21113148.
9. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
10. Real PJ, Cao Y, Wang R, Nikolovska-Coleska Z, Sanz-Ortiz J, Wang S, Fernandez-Luna JL (2004). "Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2". Cancer Res. 64 (21): 7947–53. doi:10.1158/0008-5472.CAN-04-0945. PMID 15520201.
11. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
12. Paroni G, Henderson C, Schneider C, Brancolini C (2001). "Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907–15. doi:10.1074/jbc.M011565200. PMID 11399776.
13. Gajate C, Mollinedo F (2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMID 15659383.
14. Weng C, Li Y, Xu D, Shi Y, Tang H (2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. 280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID 15637055.
15. Liu Y, Vaithiyalingam S, Shi Q, Chazin WJ, Zinkel SS (2011). "BID binds to replication protein A and stimulates ATR function following replicative stress". Mol. Cell. Biol. 31 (21): 4298–309. doi:10.1128/MCB.05737-11. PMC 3209332. PMID 21859891.
16. Singh R, Pervin S, Chaudhuri G (2002). "Caspase-8-mediated BID cleavage and release of mitochondrial cytochrome c during Nomega-hydroxy-L-arginine-induced apoptosis in MDA-MB-468 cells. Antagonistic effects of L-ornithine". J. Biol. Chem. 277 (40): 37630–6. doi:10.1074/jbc.M203648200. PMID 12145284.
17. Tang D, Lahti JM, Kidd VJ (2000). "Caspase-8 activation and bid cleavage contribute to MCF7 cellular execution in a caspase-3-dependent manner during staurosporine-mediated apoptosis". J. Biol. Chem. 275 (13): 9303–7. doi:10.1074/jbc.275.13.9303. PMID 10734071.
18. Viswanath V, Wu Y, Boonplueang R, Chen S, Stevenson FF, Yantiri F, Yang L, Beal MF, Andersen JK (2001). "Caspase-9 activation results in downstream caspase-8 activation and bid cleavage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease". J. Neurosci. 21 (24): 9519–28. doi:10.1523/JNEUROSCI.21-24-09519.2001. PMID 11739563.
19. Gu Q, Wang JD, Xia HH, Lin MC, He H, Zou B, Tu SP, Yang Y, Liu XG, Lam SK, Wong WM, Chan AO, Yuen MF, Kung HF, Wong BC (2005). "Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer". Carcinogenesis. 26 (3): 541–6. doi:10.1093/carcin/bgh345. PMID 15579484.
20. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB (2002). "Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl". Carcinogenesis. 23 (1): 143–50. doi:10.1093/carcin/23.1.143. PMID 11756235.

External links

• Human BID genome location and BID gene details page in the UCSC Genome Browser.