The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs

Significance The work by Tesfaye and colleagues defines universal and tumor type–specific features of the p53 tumor suppressor transcriptional network. This study determines a “core” signature of the p53 response across different oncogenic contexts, which defines a universal set of p53 target genes. In addition, this study clarifies the basis for outcome specificity downstream of p53 activation in different oncogenic contexts. We observe that while apoptosis in lymphoma cells is not primarily determined by p53’s transcriptional activity, p53 indirectly promotes senescence in lung adenocarcinoma and sarcoma cells by activating the cis -regulatory long noncoding RNA Pvt1b , which represses Myc levels and its proliferative function.