Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
Oncol Rep. 2011 Dec;26(6):1587-93. doi: 10.3892/or.2011.1432. Epub 2011 Aug 24.
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.
转录因子 c-Myc 先前已被证明可通过核内直接相互作用被 NEMO 磷酸化和稳定。在这里，我们表明 NEMO 诱导 c-Myc 靶蛋白 γ-谷氨酰半胱氨酸合成酶 (γ-GCS) 的上调，导致细胞内谷胱甘肽 (GSH) 水平增加和同时增强氧化还原调控能力。NEMO 增强了 c-Myc 向 γ-GCS 启动子的募集，并且 c-Myc 对于 NEMO 介导的 γ-GCS 上调是必需的。NEMO 对 c-Myc 的磷酸化和稳定使细胞对电离辐射 (IR) 更具抗性。因此，NEMO 和 c-Myc 之间的相互作用可能成为开发克服放射治疗抵抗策略的目标。
