title: c-Myb regulates cell cycle-dependent expression of Erbin: an implication for a novel function of Erbin.
abstract: In the present study, we demonstrated the cell cycle periodicity of Erbin expression with the maximal expression of Erbin in G2/M phase. A significant increase in Erbin promoter activity was observed in G2/M phase-synchronized cells. Sequence analysis revealed a c-Myb site in the core promoter region of Erbin. Mutagenesis of c-Myb consensus sequences abrogated the increased Erbin promoter activity in G2/M phase. ChIP and oligonucleotide pull-down assays validated that the recruitment of c-Myb to the consensus sequences was specific. The interaction of c-Myb with c-Myb site in the Erbin promoter was significantly enhanced in G2/M phase. Ectopic overexpression of c-Myb led to the up-regulation of Erbin promoter activity and c-Myb silencing by small interfering RNA significantly decreased Erbin protein level. Transfection of c-Myb rescued Erbin expression that was impaired by c-Myb knockdown. It proves that c-Myb and the c-Myb response element mediate the cell cycle-dependent expression of Erbin. Inactivation of Erbin causes an acceleration of the G1/S transition, the formation of multipolar spindles and abnormal chromosome congression. These results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M phase and also predict an unappreciated function of Erbin in cell cycle progression.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Qian
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Meiru
authors.initials: M
authors.lastname: Hu
authors.forename: Ruihong
authors.initials: R
authors.lastname: Zhang
authors.forename: Tianyou
authors.initials: T
authors.lastname: Wang
authors.forename: Caili
authors.initials: C
authors.lastname: Han
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002453:Cell Cycle; D045744:Cell Line, Tumor; D016384:Consensus Sequence / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C413364:ERBIN protein, human; D020598:Proto-Oncogene Proteins c-myb