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Inactivation of hTERT transcription by Tax.

Abstract：

:Telomerase expression is the hallmark of tumor cells in which this ribonucleoprotein complex preserves chromosome integrity by maintaining telomere length and thereby prevents cell death. However, recent data support a role of the combination of p53 and telomerase inactivation in initiating genetic instability that promotes malignant transformation. Through its pleiotropic effects on infected T-cell metabolism, the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax plays a central role in leukemogenesis. Here, we show that Tax inhibits human telomerase reverse transcriptase (hTERT) transcription, which is the rate-limiting factor of telomerase activity. This inhibitory effect, that occurs in competition with c-Myc through a canonical c-Myc binding site within the hTERT promoter, results in a decreased telomerase activity of Tax-expressing cells. This is the first demonstration of hTERT inhibition by an oncogene. Tax, which is only expressed in preleukemic cells, triggers infected T-cell cycle and keeps these cells cycling while inactivating p53. We propose that, in combination with these effects, hTERT repression by Tax at an early phase of carcinogenesis might contribute to the massive ploidy changes associated with the development of HTLV-1-associated malignancies.

journal_name

Oncogene

journal_title

Oncogene

authors

Gabet AS,Mortreux F,Charneau P,Riou P,Duc-Dodon M,Wu Y,Jeang KT,Wattel E

doi

10.1038/sj.onc.1206468

subject

Has Abstract

pub_date

2003-06-12 00:00:00

pages

3734-41

issue

24

eissn

0950-9232

issn

1476-5594

pii

1206468

journal_volume

22

pub_type

杂志文章

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