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- Title
Regulation of telomerase reverse transcriptase gene activity by upstream stimulatory factor.
- Authors
Goueli, Basem S.; Janknecht, Ralf
- Abstract
Upregulation of human telomerase reverse transcriptase (hTERT) transcription accounts for the immortalization of greater than 85% of all human tumor cells. However, the mechanism whereby hTERT expression is activated remains unresolved. Specifically, recent data challenging the role of Myc/Max in E-box-dependent activation of hTERT expression suggests that other E-box-binding proteins regulate hTERT transcription. Indeed, we now demonstrate that two such proteins, upstream stimulatory factor (USF) 1 and 2, readily associate with two E-boxes in the hTERT promoter in vitro and in vivo primarily as heterodimers, whereas Myc/Max does not. The avid binding of USF1/2 heterodimers to these E-boxes occurs in both hTERT-positive and -negative cells. In contrast, USF1/2 activates the hTERT promoter exclusively in hTERT-positive cells in a manner that is enhanced by the coactivator p300 and attenuated upon inhibiting p38-MAP kinase, a known modulator of USF activity. Collectively, our data indicate that USF binding to the hTERT promoter may be transcriptionally neutral, or even repressive, in nonimmortalized hTERT-negative somatic cells, but stimulatory in hTERT-positive cells where USF1/2 contributes to the acquisition and maintenance of immortality.Oncogene (2003) 22, 6098-6103. doi:10.1038/sj.onc.1206847
- Subjects
TELOMERASE; TUMORS; CANCER cells; PROTEINS; GENE expression
- Publication
Oncogene, 2003, Vol 22, Issue 39, p6098
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206847