Expanding the reach of the p53 tumor suppressor network

Lying at the heart of most human cancers is the p53 tumor suppressor pathway.1 When functional, p53 responds to a wide array of cellular stresses by inducing cell cycle arrest or apoptosis. It also facilitates DNA repair, regulates cell metabolism, blocks angiogenesis and triggers cell senescence. Therefore, it is not surprising that when p53 is mutated an emerging tumor cell, perhaps as a result of the activation of an oncogene, can continuously divide, survive and undergo metastasis. How p53 controls such essential processes to suppress tumorigenesis is primarily based on its ability to transcriptionally regulate an ever-expanding series of downstream target genes. The study by Wang et al.2 has taken an integrative genomic approach using chromatin immunoprecipitation-coupled sequencing (ChIP-seq) and transcriptome analyses to identify an extensive panel of new target genes that may mediate established p53 activities and less well-characterized p53 functions involved in cell signaling, metabolism, motility and immunity. These findings open new opportunities for advancing our understanding of how the p53 network protects against oncogenesis.