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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
8289968 - Multiple fractions of gamma rays do not induce overexpression of c-myc or c-ki-ras onco...
1328258 - Chromatin structure changes suggest a compensatory response to c-myc gene amplification...
15241468 - Myc-induced proliferation and transformation require akt-mediated phosphorylation of fo...
2674898 - Analysis of polyadenylation site usage of the c-myc oncogene.
21286748 - Flower development in garlic: the ups and downs of galfy expression.
23927648 - When the swimming gets tough, the tough form a biofilm.
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    
Affiliation:
Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF121948;  AF121949
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / metabolism*
Base Sequence
Cell Transformation, Neoplastic*
Conserved Sequence
DNA-Binding Proteins
Gene Expression Regulation
Humans
Mice
Molecular Sequence Data
Peptidylprolyl Isomerase*
Promoter Regions, Genetic
Protein Biosynthesis*
Proteins / genetics
Proto-Oncogene Proteins c-myc / metabolism*
RNA*
RNA-Directed DNA Polymerase / biosynthesis*,  genetics
Rats
Sequence Homology, Nucleic Acid
Telomerase / biosynthesis*,  genetics
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
5T32GM07491/GM/NIGMS NIH HHS; R01EY09300/EY/NEI NIH HHS; R01HD28317/HD/NICHD NIH HHS
Chemical
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 2.7.7.49/RNA-Directed DNA Polymerase; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse; EC 5.2.1.8/ILPA protein, Aeromonas hydrophila; EC 5.2.1.8/Peptidylprolyl Isomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  TIF1gamma, a novel member of the transcriptional intermediary factor 1 family.
Next Document:  Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase a...