p53 induces apoptosis by target gene regulation and transcription-independent signaling.
A fraction of induced p53 translocates to the mitochondria of apoptosing tumor cells. Targeting p53 to mitochondria is sufficient to launch apoptosis.
Evidence that p53 translocation to the mitochondria occurs in vivo in irradiatedthymocytes was shown.
Further, p53 can directly induce permeabilization of the outer mitochondrial membrane by forming complexes with the protective BCL2L1, resulting in cytochrome c release.
p53 binds to BCL2L1 via its DNA binding domain.
Tumor-derived transactivation-deficient mutants of p53 concomitantly lose the ability to interact with BCL2L1 and promote cytochrome c release.