BH3 interacting domain death agonist
From Wikipedia, the free encyclopedia
| BH3 interacting domain death agonist | |
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| Symbol(s): | BID |
| Genetic data | |
| Locus: | Chr. 22 q11.2 |
| Database Links | |
| Entrez: | 637 |
| OMIM: | 601997 |
| RefSeq: | NM_001196 |
| UniProt: | P55957 |
The BH3 interacting domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family.[1] 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 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). This results in the loss of mitochondrial membrane potential and the release of cytochrome c and other pro-apoptotic factors from the mitochondria, often referred to as mitochondrial outer membrane permeabilization, leading to activation of caspases. This defines Bid as a 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.[2] 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.
[edit] See also
- Apoptosis
- Apoptosome
- Bcl-2
- Bcl-2-associated_X_protein (BAX)
- Caspases
- Cytochrome c
- Noxa
- Mitochondrion
- p53 upregulated modulator of apoptosis (PUMA)
[edit] References
- ^ Wang, K.; Yin X. M., Chao D. T., Milliman C. L. and Korsmeyer S. J. (November 1996). "BID: a novel BH3 domain-only death agonist". Genes Dev 10: 2859-2869. PMID 8918887.
- ^ Sax, J. K.; Fei P., Murphy M. E., Bernhard E., Korsmeyer S. J. and El-Deiry W. S. (November 2002). "BID regulation by p53 contributes to chemosensitivity". Nat. Cell Biol. 4: 842–9. PMID 12402042.
