Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling

摘要: The mechanism of p53-mediated apoptosis after cellular stress remains poorly understood. Evidence suggests that p53 induces cell death by a multitude molecular pathways involving activation target genes and transcriptionally independent direct signaling. Mitochondria play key role in apoptosis. We show here fraction protein localizes to mitochondria at the onset p53-dependent but not during p53-independent or cycle arrest. accumulation is rapid (within 1 h activation) precedes changes mitochondrial membrane potential, cytochromec release, procaspase-3 activation. Immunoelectron microscopy immuno-fluorescence-activated sorter analysis isolated majority membranous compartment, whereas found complex with import motor mt hsp70. After induction ectopic without additional DNA damage p53-deficient cells, again partially mitochondria, preceding Overexpression anti-apoptotic Bcl-2 Bcl-xL abrogates signal-mediated arrest, suggesting feedback signaling loop between apoptotic regulators. Importantly, bypassing nucleus targeting using leader fusions sufficient induce cells. propose model where can contribute thereby amplifying transcription-dependent p53.