Direct activation of TERT transcription by c-MYC.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print Cited Medium: Print ISSN: 1061-4036 (Print) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Nature Pub. Co., c1992-
    • Subject Terms:
      RNA* ; Transcription, Genetic*; Genes, myc/*physiology ; Proteins/*genetics ; Proto-Oncogene Proteins c-myc/*genetics; Binding Sites/genetics ; Cell Line ; DNA-Binding Proteins ; Humans ; Promoter Regions, Genetic ; Proto-Oncogene Mas ; Telomerase/genetics ; Telomerase/metabolism
    • 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.
    • Grant Information:
      CA20525 United States CA NCI NIH HHS; CA37165 United States CA NCI NIH HHS; CA75125-01 United States CA NCI NIH HHS
    • Molecular Sequence:
      GENBANK AF114847
    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (MAS1 protein, human)
      0 (Proteins)
      0 (Proto-Oncogene Mas)
      0 (Proto-Oncogene Proteins c-myc)
      0 (telomerase RNA)
      63231-63-0 (RNA)
      EC 2.7.7.49 (TERT protein, human)
      EC 2.7.7.49 (Telomerase)
    • Publication Date:
      Date Created: 19990213 Date Completed: 19990225 Latest Revision: 20220316
    • Publication Date:
      20221213
    • Accession Number:
      10.1038/6010
    • Accession Number:
      9988278