Involvement of transcription repressor Snail in the regulation of human telomerase reverse transcriptase (hTERT) by transforming growth factor-ß.
Biochem Biophys Res Commun
; 465(1): 131-6, 2015 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-26235880
Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is the primary determinant for telomerase enzyme activity, which has been associated with cellular immortality. Expression of the hTERT gene is regulated by various extracellular (external) stimuli and is aberrantly up-regulated in more than 90% of cancers. Here we show that hTERT gene expression was repressed in response to transforming growth factor-ß (TGF-ß) by a mechanism dependent on transcription factors Snail and c-Myc. TGF-ß activated Snail and down-regulated c-Myc gene expression. In addition, ectopic expression of Snail strongly inhibited hTERT promoter activity, although co-expression of c-Myc abrogated this effect. Chromatin immunoprecipitation (ChIP) analysis revealed that TGF-ß decreased c-Myc occupancy and dramatically increased recruitment of Snail to the E-box motifs of the hTERT promoter, thereby repressing hTERT expression. Our findings suggest a dynamic alteration in hTERT promoter occupancy by Snail and c-Myc is the mechanistic basis for TGF-ß-mediated regulation of hTERT.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Queratinócitos
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Proteínas Proto-Oncogênicas c-myc
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Fator de Crescimento Transformador beta
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Telomerase
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2015
Tipo de documento:
Article