Stra13 is induced by genotoxic stress and regulates ionizing-radiation-induced apoptosis

In response to a number of genotoxic stimuli that induce DNA damage in cells, the tumour suppressor p53 is activated resulting in cell cycle arrest or apoptosis. In this study, we have identified stimulated with retinoic acid 13 (Stra13), a basic helix-loop-helix transcription factor, as a regulator of ionizing-radiation-induced apoptosis. We show that Stra13 is induced in response to several DNA-damaging agents in a p53-independent manner. Stra13-/- thymocytes show impaired apoptosis in response to ionizing radiation, and consistently, p53 levels and also expression of its key transcriptional targets Puma and Noxa are reduced in the mutant thymocytes. In vitro, Stra13 regulates p53 levels in a mouse double mutant 2 (Mdm2)-dependent manner by physically interacting with p53 and preventing Mdm2-mediated ubiquitination and nuclear export. Together, our studies provide evidence that Stra13 is involved in DNA-damage-induced apoptosis and indicate its role in tumorigenesis.