c-Myc phosphorylation is required for cellular response to oxidative stress. Academic Article uri icon

Overview

abstract

  • Aside from the well-established roles of c-Myc in the regulation of cell cycle, differentiation, and apoptosis, a recent picture is beginning to emerge linking c-Myc to the regulation of metabolic pathways. Here, we define a further function for c-Myc in determining cellular redox balance, identifying glutathione (GSH) as the leading molecule mediating this process. The link between c-Myc and GSH is gamma-glutamyl-cysteine synthetase (gamma-GCS), the rate-limiting enzyme catalyzing GSH biosynthesis. Indeed, c-Myc transcriptionally regulates gamma-GCS by binding and activating the promoters of both gamma-GCS heavy and light subunits. Exposure to H2O2 enhances c-Myc recruitment to gamma-GCS regulatory regions through ERK-dependent phosphorylation. Phosphorylation at Ser-62 is required for c-Myc recruitment to gamma-GCS promoters and determines the cellular response to oxidative stress induced by different stimuli. Thus, the c-Myc phosphorylation-dependent activation of the GSH-directed survival pathway can contribute to oxidative stress resistance in tumor cells, which generally exhibit deregulated c-Myc expression.

publication date

  • February 17, 2006

Research

keywords

  • Gene Expression Regulation, Enzymologic
  • Glutathione
  • Oxidative Stress
  • Proto-Oncogene Proteins c-myc
  • Signal Transduction

Identity

Scopus Document Identifier

  • 32444444938

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2006.01.009

PubMed ID

  • 16483932

Additional Document Info

volume

  • 21

issue

  • 4