The p53 family orchestrates the regulation of metabolism: physiological regulation and implications for cancer therapy

Abstract

The p53 family of transcription factors is essential to counteract tumour formation and progression. Although previously this was exclusively associated with the ability of the p53 family to induce cell cycle arrest and apoptosis, an increasing number of reports have now indisputably demonstrated that the tumour suppressive functions of the p53 family members also rely on their ability to control and regulate cellular metabolism and maintain cellular oxidative homeostasis. Here, we review how each p53 family member, including p63 and p73, controls metabolic pathways in physiological conditions, and how these mechanisms could be exploited to provide anticancer therapeutic opportunities.

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

“…7C). p53 has been shown to play a critical role in intrinsic tumor suppression pathways, via apoptosis induction and cell cycle arrest pathways (Napoli and Flores, 2017). One of the multiple effects of p53 is to promote apoptosis by disrupting the Bax/Bcl-2 complex and consequent activation of caspase 3.…”

HMGA2 promotes intestinal tumorigenesis by facilitating MDM2‐mediated ubiquitination and degradation of p53

“…As the most prominent tumor suppressor, p53 exerts its function by regulating the transcription of downstream genes that play important roles in diverse biological processes, including cell cycle, apoptosis, DNA damage response, and differentiation . Under physiological conditions, p53 is maintained at a very low level by ubiquitination .…”

Directin vivomapping of functional suppressors in glioblastoma genome

“…Because GBM is a disease originating from astrocytes, we generated an AAV-CRISPR vector that encodes Cre recombinase under a Glial fibrillary acidic protein (GFAP) promoter, resulting in conditional expression of Cas9 and GFP in astrocytes when injected into a conditional LSL-Cas9 mouse (Methods) ( Figure S1A). The vector also contains an sgRNA targeting Trp53, with the initial intent to generate co-mutational Trp53 knockout that might exhibit genome instability and thus be sensitized to tumorigenesis [23][24][25][26][27] . Local viral delivery into the brain restricts the number of transducible cells, and cancer genomes generally consist of dozens to hundreds of SMGs [28][29][30][31] .…”