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BAX

MIM.600040 19q13.3-q13.4

Tuesday 22 April 2008

The Bcl-2–associated X protein, or BAX, gene was the first identified pro-apoptotic member of the Bcl-2 protein 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.

The proapoptotic BAX protein induces cell death by acting on mitochondria.

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.

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 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 (CASP9).

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.

Bax (BAX) and p53 (TP53)

The expression of BAX is upregulated by the tumor suppressor protein p53 (TP53), 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.

Pathology

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