The activated Notch1 receptor cooperates with α-enolase and MBP-1 in modulating c-myc activity

Kai Wen Hsu, Rong-Hong Hsieh, Yan Hwa Wu Lee, Chi Hong Chao, Kou Juey Wu, Min Jen Tseng, Tian-Shun Tsai

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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 protooncogene. 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 α-enolase and c-myc promoter binding protein 1 (MBP-1). Both α-enolase and MBP-1 suppressed the NUC-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 α-enolase or MBP-1. Furthermore, N1IC, YY1, and α-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 α-enolase and MBP-1. In addition, both α-enolase and MBP-1 suppressed the N1IC-enhanced colony-forming ability through c-myc. These results indicate that the activated Notch1 receptor and α-enolase or MBP-1 cooperate in controlling c-myc expression through binding the YY1 response element of the c-myc promoter to regulate tumorigenesis.

Original languageEnglish
Pages (from-to)4829-4842
Number of pages14
JournalMolecular and Cellular Biology
Volume28
Issue number15
DOIs
Publication statusPublished - Aug 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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