Figure 1.

Mutant p53 binds the signal transducer DAB2IP in the cytoplasm and interferes with its functions. This favors activation of the NF-kB transcription factor and reduces activation of the ASK1/JNK kinases, resulting in a gene expression program that stimulates cell invasion and protects from cell death, thus increasing cancer aggressiveness. This same program includes expression of powerful chemokines that can recruit immune cells to the tumor, potentially improving response to therapy. ASK1, apoptosis signal regulating kinase-1; DAB2IP, disabled homolog-2 interacting protein; JNK, c-jun N-terminal kinase; mutp53, missense mutant p53; NF-κB, nuclear factor kappa-B; TNFα, tumor necrosis factor-α.