SUPEROXIDE ANION MEDIATED POST-TRANSLATIONAL REGULATION OF C-MYC ONCOPROTEIN

Abstract

Distinct regulatory pathways control c-Myc protein stability as well as its activity. While phosphorylation at Serine 62 (S62) increases c-Myc stability, phosphorylation at Threonine 58 (T58) destabilizes Myc. Phosphorylation at these sites is regulated by Ras-activated signaling pathways, the PP2A phosphatase, the Pin1 prolyl isomerase, and the Axin scaffolding protein, which coordinates these enzymes into a destruction complex for c-Myc. Moreover, recent evidence indicates that these phosphorylation sites also control c-Myc’s apoptotic and tumorigenic potential, thus coupling c-Myc stability to its function such that stabilized Myc with elevated S62 phosphorylation has increased oncogenic activity. Of particular interest is PP2A phosphatase, as we have shown in recent years that this enzyme is amenable to redox insults. My research hence revolves around the broad hypothesis of whether oxidative stress vis-à-vis, tilting the balance towards superoxide by clamping down superoxide dismuatse, could possibly contribute to engaging cancer cells into a highly proliferative stage driven primarily through an amplified c-Myc signal. This paradigm shift in our understanding of c-Myc could most certainly give us valuable cues in providing a pathway for therapeutic intervention targeting post-translational regulation of c-Myc in human cancer.