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 |
|
Language |
|
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 |
-
-
en
Nucleic acids research
-
Volume Number28
Issue Number3
Page Start669
Page End677
|
File |
|
Oaidate |
2023-07-26 |