BAX|S163_unk|T167_unk:BCL2@Mitochondrial outer membrane
The Bcl2 family proteins regulate and mediate the mitochondrial outer membrane permeabilization, a crucial event in the mitochondrial pathway of apoptosis in vertebrates.
The regulation of apoptosis is governed largely by interactions between the pro-survival and pro-death members of the Bcl2 protein family.
Some members of this family (e.g., Bax, Bak, and Bid: pro-apoptotic proteins) promote apoptosis, while others such as BCL2, BCL2L1, BCL2L2 (anti-apoptotic proteins) work against programmed cell death.
The BCL2 family proteins are characterized by regions of specific sequence homology named as BCL2 homology (BH) motifs that number from 1 to 4 and are critical for function.
Especially a helical BH3 motif of pro-apoptotic proteins occupy and form strong interactions with hydrophobic groove of anti-apoptotic BCL2 family proteins which leads to the activation of the essential death mediators Bax and Bak, thereby committing cells to apoptosis
A oncogene-derived protein, Bcl2, confers negative control in the pathway of cellular suicide machinery.
A Bcl2-homologous protein, Bax, promotes cell death by competing with Bcl2.
While Bax–Bax homodimers act as apoptosis inducers, Bcl2– Bax heterodimer formation evokes a survival signal for the cells.
Both Bcl2 and Bax are transcriptional targets for the tumour suppressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage.
Bax homodimerizes and forms heterodimers with BCL2 in vivo.
Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line.
Overexpressed Bax also counters the death repressor activity of BCL2.
These data suggest a model in which the ratio of BCL2 to Bax determines survival or death following an apoptotic stimulus.
Participates in complexes:
In compartment: Mitochondria
In compartment: Mitochondrial outer membrane
Participates in reactions:
As Reactant or Product:
- BCL2|pho@Mitochondrial outer membrane + BAX|S163_unk|T167_unk@Mitochondrial outer membrane → BAX|S163_unk|T167_unk:BCL2@Mitochondrial outer membrane
- BAX@Cytoplasm + BCL2@Mitochondria → BAX:BCL2@Mitochondria