Bcl-2-associated X protein
From Wikipedia, the free encyclopedia
| BCL2-associated X protein | |
|---|---|
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| Symbol(s): | BAX |
| Genetic data | |
| Locus: | Chr. 19 q13.3 |
| Database Links | |
| Entrez: | 581 |
| OMIM: | 600040 |
| RefSeq: | NM_138763 |
| UniProt: | P55269 |
The Bcl-2–associated X protein, or BAX, gene was the first identified 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.
Bax is a pro-apoptotic Bcl-2 protein containing BH1, BH2 and BH3 domains. In healthy mammalian cells, the majority of Bax is found in the cytosol, but upon initiation of apoptotic signaling, Bax undergoes a conformation shift, and inserts into organelle membranes, primarily the outer mitochondrial membrane.[2] 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 a direct role for Bax in mitochondrial outer membrane permeabilization, a role common to the Bcl-2 proteins containing the BH1, BH2 and BH3 domains.
The expression of BAX is upregulated by the tumor suppressor protein p53, and Bax has been shown to be involved in p53-mediated apoptosis. 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 BAX. 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
- BH3 interacting domain death agonist (BID)
- Caspases
- Cytochrome c
- Noxa
- Mitochondrion
- p53 upregulated modulator of apoptosis (PUMA)
[edit] References
- ^ Oltvai, Z. N.; Milliman, C. L. and Korsmeyer, S. J. (August 1993). "Bcl-2 Heterodimerizes In Vivo with a Conserved Homolog, Bax, That Accelerates Programed Cell Death". Cell 74: 609-619.
- ^ Wolter, K. G.; Hsu, Y., Smith, C. L., Mechushtan, A., Xi, X., and Youle, R. J. (December 1997). "Movement of Bax from Cytosol to Mitochondria during Apoptosis". Journal of Cell Biology 139: 1281-1292.
