AUTHOR=Kim Michael Paul , Zhang Yun , Lozano Guillermina 

TITLE=Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

JOURNAL=Frontiers in Oncology

VOLUME=5

YEAR=2015

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2015.00249

DOI=10.3389/fonc.2015.00249

ISSN=2234-943X

ABSTRACT=<p>The functional importance of <italic>p53</italic> as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The <italic>p53</italic> gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve <italic>p53</italic> missense mutations that result in the production of mutant <italic>p53</italic> proteins. Such mutant <italic>p53</italic> proteins lack normal <italic>p53</italic> function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant <italic>p53</italic> gain of function in various model systems. In addition, we review mutant <italic>p53</italic> addiction as emerging evidence suggests that tumors may depend on sustained mutant <italic>p53</italic> activity for continued growth. We also discuss the role of <italic>p53</italic> in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant <italic>p53</italic> in various organ systems are reviewed and their limitations discussed.</p>