Che-ating death: CHE1/AATF protects from p53-mediated apoptosis

Abstract

The tumour suppressor p53 directs cells towards different fates depending on the cell type and the stimulus. The decision to direct a cell towards apoptosis rather than cell-cycle arrest or senescence has important implications for tumour suppression in normal cells and drug response in tumour cells. Cells that undergo senescence and growth arrest can persist and contribute to organismal ageing (Campisi, 2005), or they can contribute to tumour relapse (Jackson et al, 2012). In this issue of The EMBO Journal, Höpker et al (2012) show in a comprehensive study that the RNA PolII binding protein CHE1/AATF is a factor that determines the fate of cells that have activated the p53 pathway.

Figure 1

Model of pharmacological inhibition of CHE1/AATF phosphorylation. In some cell types, following DNA damaging chemotherapy, the DDR signals to the kinase MK2 to phosphorylate CHE1/AATF, resulting in translocation to the nucleus and inhibition of p53-mediated transcription of its apoptotic target genes (A). Pharmacological inhibition of CHE1/AATF nuclear localization and binding to the p53 apoptotic target gene promoters, as depicted here with a kinase inhibitor of MK2 (KI), could increase expression of BAX, PUMA and BAK, resulting in a shift in response from arrest to cell death (B).