title: Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1.
abstract: It has been reported previously that cyclin G1 enables cells to overcome radiation-induced G(2) arrest and increased cell death and that these effects are mediated by transcriptional activation of cyclin B1. In this study, we further investigated the mechanism by which cyclin G1 transcriptionally activates cyclin B1. Deletion or point mutations within the cyclin B1 promoter region revealed that the c-Myc binding site (E-box) is necessary for cyclin G1-mediated transcriptional activation of cyclin B1 to occur. In addition, the kinase activity of Cdk5 was increased by cyclin G1 overexpression, and Cdk5 directly phosphorylated c-Myc on Ser-62. Furthermore, cyclin G1 mediated increased radiosensitivity, and radiation-induced M phase arrest was attenuated when RNA interference of Cdk5 was treated. Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1.
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Korea.
authors.forename: Haeng Ran
authors.initials: HR
authors.lastname: Seo
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Bae
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Soh
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D017354:Point Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D019926:Cyclin B; D016271:Proto-Oncogene Proteins c-myc; D012694:Serine; D051360:Cyclin-Dependent Kinase 5