Phosphorylation and stabilization of c-Myc by NEMO renders cells resistant to ionizing radiation through up-regulation of γ-GCS.

Abstract

The transcription factor c-Myc has been previously shown to be phosphorylated and stabilized by NEMO through direct interaction in the nucleus. Here, we show that NEMO induces up-regulation of the c-Myc target protein, γ-glutamyl-cysteine synthetase (γ-GCS), leading to an increase of intracellular glutathione (GSH) levels and simultaneous enhancement of redox-controlling capacity. NEMO enhanced c-Myc recruitment to γ-GCS promoters and c-Myc was essential for NEMO-mediated γ-GCS up-regulation. The phosphorylation and stabilization of c-Myc by NEMO rendered cells more resistant to ionizing radiation (IR). Thus, the interaction between NEMO and c-Myc may be targeted for the development of strategies to overcome the resistance to radiotherapy.

DOI: 10.3892/or.2011.1432
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@article{Kim2011PhosphorylationAS, title={Phosphorylation and stabilization of c-Myc by NEMO renders cells resistant to ionizing radiation through up-regulation of γ-GCS.}, author={Bu-Yeon Kim and Seo-Young Kwak and Ji-Sook Yang and Young-Hoon Han}, journal={Oncology reports}, year={2011}, volume={26 6}, pages={1587-93} }