OPTIMIZED p53 PEPTIDES WITH MITOCHONDRIAL TARGETING SIGNALS

p53 is a transcription factor that also stimulates apoptotic signaling through death receptors and the mitochondria. Over half of all cancer express p53 mutations and recombinant p53 is often introduced into cancer cells for treatment. Mutated p53, however, interacts with the introduced p53 rendering it ineffective at suppressing tumors.
p53 peptides with mitochondrial targeting signals (p53-MTS) can be introduced into tumor cells, which does not interact with mutant p53. The mitochondrial p53 works as a monomer with pro- and anti-apoptotic proteins at the mitochondrial outer membrane, causing a rapid apoptotic response. The p53-MTS and DNA binding domain constructs are active in cancer cells independent of their p53 status.