BH3 interacting-domain death agonist

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){{cite book|last=Weinberg|first=Robert A.|title=The biology of cancer|year=2007|publisher=Taylor & Francis|location=New York|isbn=978-0-8153-4076-8|pages=341}} from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of caspases (not to be confused with capsaicin). 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.{{cn|date=November 2024}}

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.{{cn|date=November 2024}}

The expression of BID is upregulated by the tumor suppressor p53, and BID has been shown to be involved in p53-mediated apoptosis.{{cite journal | vauthors = Sax JK, Fei P, Murphy ME, Bernhard E, Korsmeyer SJ, El-Deiry WS | title = BID regulation by p53 contributes to chemosensitivity | journal = Nat. Cell Biol. | volume = 4 | issue = 11 | pages = 842–9 | year = 2002 | pmid = 12402042 | doi = 10.1038/ncb866 | s2cid = 2206946 }} 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.{{cn|date=November 2024}}

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

• ATR/ATRIP,{{cite journal | vauthors = Liu Y, Bertram CC, Shi Q, Zinkel SS | title = Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress | journal = Cell Death Differ. | volume = 18 | issue = 5 | pages = 841–52 | year = 2011 | pmid = 21113148 | pmc = 3074003 | doi = 10.1038/cdd.2010.151 }}
• BCL2,{{cite journal | vauthors = Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC | title = Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function | journal = Mol. Cell | volume = 17 | issue = 3 | pages = 393–403 | year = 2005 | pmid = 15694340 | doi = 10.1016/j.molcel.2004.12.030 | doi-access = free }}{{cite journal | vauthors = Real PJ, Cao Y, Wang R, Nikolovska-Coleska Z, Sanz-Ortiz J, Wang S, Fernandez-Luna JL | title = Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2 | journal = Cancer Res. | volume = 64 | issue = 21 | pages = 7947–53 | year = 2004 | pmid = 15520201 | doi = 10.1158/0008-5472.CAN-04-0945 | doi-access = free }}
• CASP2,{{cite journal | vauthors = Paroni G, Henderson C, Schneider C, Brancolini C | title = Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3 | journal = J. Biol. Chem. | volume = 276 | issue = 24 | pages = 21907–15 | year = 2001 | pmid = 11399776 | doi = 10.1074/jbc.M011565200 | doi-access = free }}
• CASP8,{{cite journal | vauthors = Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES | title = Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria | journal = J. Biol. Chem. | volume = 277 | issue = 16 | pages = 13430–7 | year = 2002 | pmid = 11832478 | doi = 10.1074/jbc.M108029200 | doi-access = free }}{{cite journal | vauthors = Gajate C, Mollinedo F | title = Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy | journal = J. Biol. Chem. | volume = 280 | issue = 12 | pages = 11641–7 | year = 2005 | pmid = 15659383 | doi = 10.1074/jbc.M411781200 | doi-access = free }}
• MCL1,{{cite journal | vauthors = Weng C, Li Y, Xu D, Shi Y, Tang H | title = Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells | journal = J. Biol. Chem. | volume = 280 | issue = 11 | pages = 10491–500 | year = 2005 | pmid = 15637055 | doi = 10.1074/jbc.M412819200 | doi-access = free }} and
• RPA.{{cite journal | vauthors = Liu Y, Vaithiyalingam S, Shi Q, Chazin WJ, Zinkel SS | title = BID binds to replication protein A and stimulates ATR function following replicative stress | journal = Mol. Cell. Biol. | volume = 31 | issue = 21 | pages = 4298–309 | year = 2011 | pmid = 21859891 | pmc = 3209332 | doi = 10.1128/MCB.05737-11 }}

File:Casp8-BID.gif

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.{{cite journal | vauthors = Singh R, Pervin S, Chaudhuri G | title = 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 | journal = J. Biol. Chem. | volume = 277 | issue = 40 | pages = 37630–6 | year = 2002 | pmid = 12145284 | doi = 10.1074/jbc.M203648200 | doi-access = free }} Activation of caspase-8, and subsequent BID cleavage participate in cytochrome-c mediated apoptosis.{{cite journal | vauthors = Tang D, Lahti JM, Kidd VJ | title = Caspase-8 activation and bid cleavage contribute to MCF7 cellular execution in a caspase-3-dependent manner during staurosporine-mediated apoptosis | journal = J. Biol. Chem. | volume = 275 | issue = 13 | pages = 9303–7 | year = 2000 | pmid = 10734071 | doi = 10.1074/jbc.275.13.9303 | doi-access = free }} 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.{{cite journal | vauthors = Viswanath V, Wu Y, Boonplueang R, Chen S, Stevenson FF, Yantiri F, Yang L, Beal MF, Andersen JK | title = 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 | journal = J. Neurosci. | volume = 21 | issue = 24 | pages = 9519–28 | year = 2001 | pmid = 11739563 | doi = 10.1523/JNEUROSCI.21-24-09519.2001| pmc = 6763046 | doi-access = free }} 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.{{cite journal | vauthors = 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 | title = Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer | journal = Carcinogenesis | volume = 26 | issue = 3 | pages = 541–6 | year = 2005 | pmid = 15579484 | doi = 10.1093/carcin/bgh345 | doi-access = free }}{{cite journal | vauthors = Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB | title = 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 | journal = Carcinogenesis | volume = 23 | issue = 1 | pages = 143–50 | year = 2002 | pmid = 11756235 | doi = 10.1093/carcin/23.1.143 | doi-access = free }}

{{columns-list|colwidth=30em|

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

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{{Reflist}}

• {{UCSC gene info|BID}}

{{Fas apoptosis signaling pathway}}

{{DEFAULTSORT:Bh3 Interacting-Domain Death Agonist}}

Category:Apoptosis

Category:Programmed cell death

Category:Proteins