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c-Myc Phosphorylation Is Required for Cellular Response to Oxidative Stress
- Source :
-
Molecular Cell . Feb2006, Vol. 21 Issue 4, p509-519. 11p. - Publication Year :
- 2006
-
Abstract
- Summary: 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 γ-glutamyl-cysteine synthetase (γ-GCS), the rate-limiting enzyme catalyzing GSH biosynthesis. Indeed, c-Myc transcriptionally regulates γ-GCS by binding and activating the promoters of both γ-GCS heavy and light subunits. Exposure to H2O2 enhances c-Myc recruitment to γ-GCS regulatory regions through ERK-dependent phosphorylation. Phosphorylation at Ser-62 is required for c-Myc recruitment to γ-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. [Copyright &y& Elsevier]
- Subjects :
- *CELL cycle
*APOPTOSIS
*OXIDATIVE stress
*BIOCHEMISTRY
Subjects
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 21
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 19771874
- Full Text :
- https://doi.org/10.1016/j.molcel.2006.01.009