Deconstructing networks of p53-mediated tumor suppression in vivo

• Published in: Cell death and differentiation Vol. 25; no. 1; pp. 93 - 103
• Main Authors: Kaiser, Alyssa M, Attardi, Laura D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2018; Nature Publishing Group
• Subjects: 13; 64; 64/60; 692/308/1426; 692/699/67/70; Activation; Animal models; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell cycle; Cell Cycle Analysis; Cell Cycle Checkpoints; Cellular Senescence; DNA damage; DNA Repair; Hypoxia; Life Sciences; Metastases; Mice; Mice, Knockout; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; p53 Protein; Review; Senescence; Stem Cells; Transcriptional Activation; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Protein p53 - physiology; Tumorigenesis
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2017.171

The transcription factor p53 is a vital tumor suppressor. Upon activation by diverse stresses including oncogene activation, DNA damage, hypoxia and nutrient deprivation, p53 activates a panoply of target genes and orchestrates numerous downstream responses that suppress tumorigenesis. Although early studies of p53 suggested that its ability to induce cell cycle arrest, senescence and apoptosis programs accounted for its tumor-suppressor activity, more recent studies have challenged this notion. Moreover, p53 regulates a suite of additional processes, such as metabolism, stem cell function, invasion and metastasis. The processes p53 coordinately regulates to enact tumor suppression, and how such regulation occurs, thus remain elusive. In this review, we will summarize our current knowledge of p53-mediated tumor-suppressive mechanisms gleaned from
in vivo
studies in mouse models.