Apoptosis regulator BAX also known as bcl-2-like protein 4 is a protein that in humans is encoded by the BAX gene.
BAX is a member of the Bcl-2 gene family. Apoptosis regulator BAX promotes apoptosis by binding to and antagonizing the Bcl-2 protein.
The BAX gene was the first identified pro-apoptotic member of the Bcl-2protein family. 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.
Orthologs of the BAX gene  have been identified in most mammals for which complete genome data are available. Certain members of the BCL-2 protein family, such as Bcl-2, Bcl-xl and Mcl-1 are anti-apoptotic, whilst others are pro-apoptotic. 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 conformational shift. Upon induction of apoptosis, BAX becomes organelle membrane-associated, and in particular, mitochondrial membrane associated.
BAX is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence also suggests 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 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. Wild-type p53 has been demonstrated to upregulate the transcription of a chimeric reporter plasmid utilizing the consensus promoter sequence of BAX approximately 50-fold over mutant p53. Thus it is likely that p53 promotes BAX's apoptotic faculties in vivo as a primary transcription factor. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting its activation as well as its insertion into the mitochondrial membrane.
Binding of HA-BAD to BCL-xL and concomitant disruption of BAX:BCL-xL interaction was found to partly reverse paclitaxel resistance in human ovarian cancer cells.
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