Document Detail

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation.
MedLine Citation:
PMID:  10022128     Owner:  NLM     Status:  MEDLINE    
The telomerase reverse transcriptase component (TERT) is not expressed in most primary somatic human cells and tissues, but is upregulated in the majority of immortalized cell lines and tumors. Here, we identify the c-Myc transcription factor as a direct mediator of telomerase activation in primary human fibroblasts through its ability to specifically induce TERT gene expression. Through the use of a hormone inducible form of c-Myc (c-Myc-ER), we demonstrate that Myc-induced activation of the hTERT promoter requires an evolutionarily conserved E-box and that c-Myc-ER-induced accumulation of hTERT mRNA takes place in the absence of de novo protein synthesis. These findings demonstrate that the TERT gene is a direct transcriptional target of c-Myc. Since telomerase activation frequently correlates with immortalization and telomerase functions to stabilize telomers in cycling cells, we tested whether Myc-induced activation of TERT gene expression represents an important mechanism through which c-Myc acts to immortalize cells. Employing the rat embryo fibroblast cooperation assay, we show that TERT is unable to substitute for c-Myc in the transformation of primary rodent fibroblasts, suggesting that the transforming activities of Myc extend beyond its ability to activate TERT gene expression and hence telomerase activity.
R A Greenberg; R C O'Hagan; H Deng; Q Xiao; S R Hann; R R Adams; S Lichtsteiner; L Chin; G B Morin; R A DePinho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-02     Completed Date:  1999-03-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1219-26     Citation Subset:  IM    
Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF121948;  AF121949
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MeSH Terms
Bacterial Proteins / metabolism*
Base Sequence
Cell Transformation, Neoplastic*
Conserved Sequence
DNA-Binding Proteins
Gene Expression Regulation
Molecular Sequence Data
Peptidylprolyl Isomerase*
Promoter Regions, Genetic
Protein Biosynthesis*
Proteins / genetics
Proto-Oncogene Proteins c-myc / metabolism*
RNA-Directed DNA Polymerase / biosynthesis*,  genetics
Sequence Homology, Nucleic Acid
Telomerase / biosynthesis*,  genetics
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Bacterial Proteins; 0/DNA-Binding Proteins; 0/Proteins; 0/Proto-Oncogene Proteins c-myc; 0/telomerase RNA; 63231-63-0/RNA; EC DNA Polymerase; EC protein, human; EC; EC protein, mouse; EC protein, Aeromonas hydrophila; EC Isomerase

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