Direct activation of TERT transcription by c-MYC.

Details

Serval ID
serval:BIB_12423
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Direct activation of TERT transcription by c-MYC.
Journal
Nature Genetics
Author(s)
Wu K.J., Grandori C., Amacker M., Simon-Vermot N., Polack A., Lingner J., Dalla-Favera R.
ISSN
1061-4036
Publication state
Published
Issued date
1999
Volume
21
Number
2
Pages
220-224
Language
english
Notes
Publication types: Journal Article
Abstract
The MYC proto-oncogene encodes a ubiquitous transcription factor (c-MYC) involved in the control of cell proliferation and differentiation. Deregulated expression of c-MYC caused by gene amplification, retroviral insertion, or chromosomal translocation is associated with tumorigenesis. The function of c-MYC and its role in tumorigenesis are poorly understood because few c-MYC targets have been identified. Here we show that c-MYC has a direct role in induction of the activity of telomerase, the ribonucleoprotein complex expressed in proliferating and transformed cells, in which it preserves chromosome integrity by maintaining telomere length. c-MYC activates telomerase by inducing expression of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase complex activity is dependent on TERT, a specialized type of reverse transcriptase. TERT and c-MYC are expressed in normal and transformed proliferating cells, downregulated in quiescent and terminally differentiated cells, and can both induce immortalization when constitutively expressed in transfected cells. Consistent with the recently reported association between MYC overexpression and induction of telomerase activity, we find here that the TERT promoter contains numerous c-MYC-binding sites that mediate TERT transcriptional activation. c-MYC-induced TERT expression is rapid and independent of cell proliferation and additional protein synthesis, consistent with direct transcriptional activation of TERT. Our results indicate that TERT is a target of c-MYC activity and identify a pathway linking cell proliferation and chromosome integrity in normal and neoplastic cells.
Keywords
Binding Sites/genetics, Cell Line, DNA-Binding Proteins, Genes, myc/physiology, Humans, Promoter Regions, Genetic, Proteins/genetics, Proto-Oncogene Proteins c-myc/genetics, RNA, Telomerase/genetics, Telomerase/metabolism, Transcription, Genetic
Pubmed
Web of science
Create date
19/11/2007 12:03
Last modification date
20/08/2019 12:40
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