The activated Notch1 receptor cooperates with alpha-enolase and MBP-1 in modulating c-myc activity.
The Notch signal pathway plays multifaceted roles to promote or suppress tumorigenesis. The Notch1 receptor intracellular domain (N1IC), the activated form of the Notch1 receptor, activates the c-myc proto-oncogene. The complex of N1IC and transcription factor YY1 binds to the human c-myc promoter to enhance c-myc expression in a CBF1-independent manner. Here we demonstrated that N1IC interacted with the c-Myc-regulating proteins alpha-enolase and c-myc promoter binding protein 1 (MBP-1). Both alpha-enolase and MBP-1 suppressed the N1IC-enhanced activity of the c-myc promoter in a CBF1-independent manner. The YY1 response element in front of the P2 c-myc promoter was essential and sufficient for the modulation of c-myc by N1IC and alpha-enolase or MBP-1. Furthermore, N1IC, YY1, and alpha-enolase or MBP-1 but not CBF1 bound to the c-myc promoter through associating with the YY1 response element. Hemin-induced erythroid differentiation was suppressed by N1IC in K562 cells. This suppression was relieved by the expression of alpha-enolase and MBP-1. In addition, both alpha-enolase and MBP-1 suppressed the N1IC-enhanced colony-forming ability through c-myc. These results indicate that the activated Notch1 receptor and alpha-enolase or MBP-1 cooperate in controlling c-myc expression through binding the YY1 response element of the c-myc promoter to regulate tumorigenesis.
Hsu
Kai-Wen
KW
Department of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 112, Taiwan.
Hsieh
Rong-Hong
RH
Lee
Yan-Hwa Wu
YH
Chao
Chi-Hong
CH
Wu
Kou-Juey
KJ
Tseng
Min-Jen
MJ
Yeh
Tien-Shun
TS
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; C088830:DENND4A protein, human; D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; C497570:RBPJ protein, human; D051881:Receptor, Notch1; D025521:Tumor Suppressor Proteins; D050986:YY1 Transcription Factor; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase