title: 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.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological                     and Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Bu-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Kwak
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Yang
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D055550:Protein Stability; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C491731:IKBKG protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D051550:I-kappa B Kinase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione