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Title
  • en Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).
Creator
Accessrights open access
Subject
  • MeSH en Base Sequence
  • MeSH en Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MeSH en Basic-Leucine Zipper Transcription Factors
  • MeSH en Binding, Competitive
  • MeSH en Cell Line, Transformed
  • MeSH en Cell Transformation, Neoplastic/genetics
  • MeSH en Consensus Sequence/genetics
  • MeSH en DNA-Binding Proteins/genetics
  • MeSH en DNA-Binding Proteins/metabolism
  • MeSH en Dimerization
  • MeSH en Fibroblasts/enzymology
  • MeSH en Fibroblasts/metabolism
  • MeSH en Fibroblasts/pathology
  • MeSH en Humans
  • MeSH en Molecular Sequence Data
  • MeSH en Mutation/genetics
  • MeSH en Oligodeoxyribonucleotides/genetics
  • MeSH en Oligodeoxyribonucleotides/metabolism
  • MeSH en Promoter Regions, Genetic/genetics
  • MeSH en Proto-Oncogene Proteins c-myc/genetics
  • MeSH en Proto-Oncogene Proteins c-myc/metabolism
  • MeSH en Repressor Proteins/genetics
  • MeSH en Repressor Proteins/metabolism
  • MeSH en Response Elements/genetics
  • MeSH en Sp1 Transcription Factor/genetics
  • MeSH en Sp1 Transcription Factor/metabolism
  • MeSH en Telomerase/genetics
  • MeSH en Telomerase/metabolism
  • MeSH en Transcription Factors
  • MeSH en Transcriptional Activation/genetics
  • MeSH en Transfection
  • MeSH en Tumor Cells, Cultured
  • NDC 499
Description
  • Abstract en Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. The human telomerase catalytic subunit (hTERT) is a rate limiting determinant of the enzymatic activity of human telomerase. In the previous study, we identified the proximal 181 bp core promoter responsible for transcriptional activity of the hTERT gene. To identify the regulatory factors of transcription, transient expression assays were performed using hTERT promoter reporter plasmids. Serial deletion assays of the core promoter revealed that the 5'-region containing the E-box, which binds Myc/Max, as well as the 3'-region containing the GC-box, which binds Sp1, are essential for transactivation. The mutations introduced in the E-box or GC-box significantly decreased transcriptional activity of the promoter. Overexpression of Myc/Max or Sp1 led to significant activation of transcription in a cell type-specific manner, while Mad/Max introduction repressed it. However, the effects of Myc/Max on transactivation were marginal when Sp1 sites were mutated. Western blot analysis using various cell lines revealed a positive correlation between c-Myc and Sp1 expression and transcriptional activity of hTERT. Using fibroblast lineages in different stages of transformation, we found that c-Myc and Sp1 were induced to a dramatic extent when cells overcame replicative senescence and obtained immortal characteristics, in association with telomerase activation. These findings suggest that c-Myc and Sp1 cooperatively function as the major determinants of hTERT expression, and that the switching functions of Myc/Max and Mad/Max might also play roles in telomerase regulation.
Publisher en Oxford University Press
Date
    Issued2000-02-01
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/53970
Relation
  • isIdenticalTo DOI https://doi.org/10.1093/nar/28.3.669
  • PMID 10637317
Journal
    • PISSN 1362-4962
      • en Nucleic acids research
      • Volume Number28 Issue Number3 Page Start669 Page End677
File
Oaidate 2023-07-26