Che-1 Promotes Tumor Cell Survival by Sustaining Mutant p53 Transcription and Inhibiting DNA Damage Response Activation

SummaryChe-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53.

► Che-1 sustains mutant p53 expression
► Inhibition of Che-1 selectively kills tumor cells carrying mutant p53
► Inhibition of Che-1 induces DNA damage in cancer cells expressing mutant p53
► These findings suggest a therapeutic approach against tumors harboring mutant p53