to activation of caspases. This defines a direct role for BAX in mitochondrial outer membrane permeabilization. BAX activation is stimulated by various abiotic factors, including heat, hydrogen peroxide, low or high pH, and mitochondrial membrane remodeling. In addition, it can become activated by binding BCL-2, as well as non-BCL-2 proteins such as p53 and Bif-1. Conversely, BAX can become inactivated by interacting with VDAC2, Pin1, and IBRDC2. Clinical significance 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. Drugs that activate BAX, such as ABT-737, a BH3 mimetic, hold promise as anticancer treatments by inducing apoptosis in cancer cells. For instance, 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. Meanwhile, excessive apoptosis in such conditions as ischemia reperfusion injury and amyotrophic lateral sclerosis may benefit from drug inhibitors of BAX. Interactions Bcl-2-associated X protein has been shown to interact with: Bcl-2, BCL2L1, BCL2A1 SH3GLB1, SLC25A4, VDAC1, TCTP, YWHAQ, Bid, Bim, Puma, Noxa, Mfn2, cholesterol, and cardiolipin. See also Apoptosis Apoptosome Bcl-2 BH3 interacting domain death agonist (BID) Caspases Cytochrome c Noxa Mitochondrion p53 upregulated modulator of apoptosis (PUMA) References External links Apoptosis Programmed cell death Proteins