A novel link between p53 and ROS

As one of the most intensively studied transcription factors, it is unsurprising that p53 is involved in many biological processes, including cell cycle arrest, DNA repair, senescence and apoptosis.1 its activities are mainly regulated by posttranslational modifications and interactions with other cellular components. Over the past few years, p53 has also been linked to redox homeostasis, the balance between cellular proand antioxidant levels.2 On the one hand, reactive oxygen species (ROs) can modify the cysteine residues of p53, leading to a conformational change that affects its transcriptional activities.2 On the other hand, p53 also acts as an upstream regulator of ROs production by activating or repressing several ROs-regulating genes, such as glutathine peroxidase (GPX), p53-induced genes (PiGs), nitric oxide synthase 2 (NOs2) and Mn superoxide dismutase (MnsOD).2 Those genes have been shown to act either in a proor an antioxidant context. Hence, the role of p53 in overall ROs regulation is a complex network and still needs to be investigated in depth. ROs are generated by both mitochondrial and non-mitochondrial pathways. in the latter pathway, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) mainly contributes to ROs production. Among many family members, NOX2 is the one which has been most extensively studied (Fig. 1). NOX2 mainly localizes on the plasma membrane and generates superoxide utilizing NADPH and molecular oxygen upon activation, e.g., in the process of phagocytosis.3 Recently, neutrophil cytosolic factor 2 (NCF2), the gene encoding p67phox, which is the cytosolic subunit and activator of NOX2, has been identified as a novel target of p53.4 in this study, italiano et al. have shown that p53 can bind to the promoter of NCF2 and activate gene expression, indicating that p53 is a transcription factor for NOX2. NCF2 is upregulated by doxorubicin treatment in p53-positive HCT 116 cells but Cell Cycle News & Views