AUTHOR=Nagpal Isha , Yuan Zhi-Min 

TITLE=The Basally Expressed p53-Mediated Homeostatic Function

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.775312

DOI=10.3389/fcell.2021.775312

ISSN=2296-634X

ABSTRACT=Apart from mutations in the p53 gene, p53 functions can be alternatively compromised by a decrease in nuclear p53 protein levels or activities. In accordance, enhanced p53 protein turnover due to elevated expression of the critical p53 E3 ligase MDM2 or MDM2/MDMX is found in many human cancers. Likewise, the HPV viral E6 protein-mediated p53 degradation critically contributes to the tumorigenesis of cervical cancer. In addition, growth-promoting signaling-induced cell proliferation is accompanied by p53 downregulation. Animal studies have also shown that loss of p53 is essential for oncogenes to drive malignant transformation. The close association between p53 downregulation and carcinogenesis implicates a critical role of basally expressed p53. In accordance, available evidence indicates that a reduced level of basal p53 is usually associated with disruption of homeostasis, suggesting a homeostatic function of basally expressed p53. However, challenging to investigate due to its relatively low level with little transcriptional activity, basal p53 remains not completely understood.  Thus, a critical question is whether basal expressed p53 may have transcription-independent activities. In this review, we summarize the findings pertinent to basal p53-mediated activities in the hope of developing a model in which basally expressed p53 functions as a barrier to anabolic metabolism to preserve homeostasis. A better understanding of this homeostatic function of p53 may offer novel insight into the role of p53 in tumor suppression.