TY - JOUR
T1 - P53
T2 - Multiple facets of a rubik's cube
AU - Zhang, Yun
AU - Lozano, Guillermina
N1 - Publisher Copyright:
© 2017 by Annual Reviews. All rights reserved.
PY - 2017
Y1 - 2017
N2 - The p53 tumor suppressor has been studied for decades, and still there are many questions left unanswered. In this review, we first describe the current understanding of the wild-Type p53 functions that determine cell survival or death, and regulation of the protein, with a particular focus on the negative regulators, the murine double minute family of proteins. We also summarize tissue-, stress-, and age-specific p53 activities and the potential underlying mechanisms. Among all p53 gene alterations identified in human cancers, p53 missense mutations predominate, suggesting an inherent biological advantage. Numerous gain-of-function activities of mutant p53 in different model systems and contexts have been identified. The emerging theme is that mutant p53, which retains a potent transcriptional activation domain, also retains the ability to modify gene transcription, albeit indirectly. Lastly, because mutant p53 stability is necessary for its gain of function, we summarize the mechanisms through which mutant p53 is specifically stabilized. A deeper understanding of the multiple pathways that impinge upon wild-Type and mutant p53 activities and how these, in turn, regulate cell behavior will help identify vulnerabilities and therapeutic opportunities.
AB - The p53 tumor suppressor has been studied for decades, and still there are many questions left unanswered. In this review, we first describe the current understanding of the wild-Type p53 functions that determine cell survival or death, and regulation of the protein, with a particular focus on the negative regulators, the murine double minute family of proteins. We also summarize tissue-, stress-, and age-specific p53 activities and the potential underlying mechanisms. Among all p53 gene alterations identified in human cancers, p53 missense mutations predominate, suggesting an inherent biological advantage. Numerous gain-of-function activities of mutant p53 in different model systems and contexts have been identified. The emerging theme is that mutant p53, which retains a potent transcriptional activation domain, also retains the ability to modify gene transcription, albeit indirectly. Lastly, because mutant p53 stability is necessary for its gain of function, we summarize the mechanisms through which mutant p53 is specifically stabilized. A deeper understanding of the multiple pathways that impinge upon wild-Type and mutant p53 activities and how these, in turn, regulate cell behavior will help identify vulnerabilities and therapeutic opportunities.
KW - Age specificity
KW - Gain of function
KW - Missense mutation
KW - P53 stabilization
KW - Stress specificity
KW - Tissue specificity
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U2 - 10.1146/annurev-cancerbio-050216-121926
DO - 10.1146/annurev-cancerbio-050216-121926
M3 - Article
C2 - 30775651
AN - SCOPUS:85048936750
SN - 2472-3428
VL - 1
SP - 185
EP - 201
JO - Annual Review of Cancer Biology
JF - Annual Review of Cancer Biology
ER -