BBC3 (so-called PUMA, p53 upregulated modulator of apoptosis) as a target for activation by p53.
This gene encodes two BH3 domain–containing proteins that are induced in cells following p53 activation.
BBC3 binds to BCL2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death.
Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role inmediating p53-induced cell death through the cytochrome c/Apaf-1–dependent pathway.
PUMA was found to be exclusively mitochondrial and to bind to BCL2 and BCL2L1 through a BH3 domain.
It is via this binding to BBC3 (an apoptic inducer) that BCL2 and BCL2L1 exhibit their anti-apoptic effect.