Direct activation of TERT transcription by c-MYC
The MYC proto-oncogene encodes a ubiquitous transcription factor (c–MYC) involved in the control of cell proliferation and differentiation 1 . Deregulated expression of c–MYC caused by gene amplification, retroviral insertion, or chromosomal translocation is associated with tumorigenesis 2 . The fun...
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Veröffentlicht in: | Nature genetics 1999-02, Vol.21 (2), p.220-224 |
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Zusammenfassung: | The
MYC
proto-oncogene encodes a ubiquitous transcription factor (c–MYC) involved in the control of cell proliferation and differentiation
1
. Deregulated expression of c–MYC caused by gene amplification, retroviral insertion, or chromosomal translocation is associated with tumorigenesis
2
. The function of c–MYC and its role in tumorigenesis are poorly understood because few c–MYC targets have been identified
3
. 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
4
,
5
,
6
. c–MYC activates telomerase by inducing expression of its catalytic subunit, telomerase reverse transcriptase
7
,
8
,
9
(TERT). Telomerase complex activity is dependent on TERT, a specialized type of reverse transcriptase
10
,
11
. TERT and c–MYC are expressed in normal and transformed proliferating cells, downregulated in quiescent and terminally differentiated cells
1
,
9
,
12
,
13
, and can both induce immortalization when constitutively expressed in transfected cells
2
,
10
,
11
. Consistent with the recently reported association between
MYC
overexpression and induction of telomerase activity
14
, 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. |
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ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/6010 |