000114176 001__ 114176
000114176 005__ 20181203021019.0
000114176 037__ $$aARTICLE
000114176 245__ $$aDirect activation of TERT transcription by c-MYC
000114176 269__ $$a1999
000114176 260__ $$c1999
000114176 336__ $$aJournal Articles
000114176 520__ $$aThe 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.
000114176 700__ $$aWu, K. J.
000114176 700__ $$aGrandori, C.
000114176 700__ $$aAmacker, M.
000114176 700__ $$aSimon-Vermot, N.
000114176 700__ $$aPolack, A.
000114176 700__ $$0240570$$g168670$$aLingner, J.
000114176 700__ $$aDalla-Favera, R.
000114176 773__ $$j21$$tNat Genet$$k2$$q220-4
000114176 909C0 $$xU11159$$0252147$$pUPLIN
000114176 909CO $$pSV$$particle$$ooai:infoscience.tind.io:114176
000114176 937__ $$aUPLIN-ARTICLE-1999-001
000114176 970__ $$a51/UPLIN
000114176 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000114176 980__ $$aARTICLE