Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr;73(8):1659-70.
doi: 10.1007/s00018-016-2146-9. Epub 2016 Feb 4.

Reactivation of telomerase in cancer

Semih Can Akincilar  1   2 , Bilal Unal  1   2 , Vinay Tergaonkar  3   4   5
Affiliations
Review

Reactivation of telomerase in cancer

Semih Can Akincilar et al. Cell Mol Life Sci. 2016 Apr.

Abstract

Activation of telomerase is a critical step in the development of about 85 % of human cancers. Levels of Tert, which encodes the reverse transcriptase subunit of telomerase, are limiting in normal somatic cells. Tert is subjected to transcriptional, post-transcriptional and epigenetic regulation, but the precise mechanism of how telomerase is re-activated in cancer cells is poorly understood. Reactivation of the Tert promoter involves multiple changes which evolve during cancer progression including mutations and chromosomal re-arrangements. Newly described non-coding mutations in the Tert promoter region of many cancer cells (19 %) in two key positions, C250T and C228T, have added another layer of complexity to telomerase reactivation. These mutations create novel consensus sequences for transcription factors which can enhance Tert expression. In this review, we will discuss gene structure and function of Tert and provide insights into the mechanisms of Tert reactivation in cancers, highlighting the contribution of recently identified Tert promoter mutations.

Keywords: Cancer; NF-κB; TERT reactivation; Tert promoter mutation; Transcription.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic of Tert promoter region with regulatory protein binding sites and de-novo mutations. The +1 and +78 (ATG) indicates transcription start site (TSS) and first codon for TERT protein, respectively. Dark blue regions correspond to CpG islands. Highly recurrent mutations C228T and C250T are shown at −46 and −68 positions from TSS. The rs2853669 polymorphism is shown in ETS2 binding site (−167 from TSS). The sites on the promoter are not precisely scaled
Fig. 2
Fig. 2
Highly recurrent mutations C228T and C250T create novel ETS binding sites in Tert promoter. Tert promoter with wild type, C250T and C228T are shown with their reported binding partners. Red and green rectangular boxes indicate ETS and p52 consensus sites on Tert promoter, respectively. ETS1/2 and p52 binds Tert promoter harboring C250T mutation while GABP binds to Tert promoter bearing either C250T or C228T mutation, resulting in increased Tert mRNA expression
See this image and copyright information in PMC

References

    1. Moyzis RK, et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA. 1988;85:6622–6626. doi: 10.1073/pnas.85.18.6622. - DOI - PMC - PubMed
    1. Blackburn EH. The end of the (DNA) line. Nat Struct Biol. 2000;7:847–850. doi: 10.1038/79594. - DOI - PubMed
    1. Watson JD. Origin of concatemeric T7 DNA. Nature New Biol. 1972;239:197–201. doi: 10.1038/newbio239197a0. - DOI - PubMed
    1. Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol. 1973;41:181–190. doi: 10.1016/0022-5193(73)90198-7. - DOI - PubMed
    1. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985;43:405–413. doi: 10.1016/0092-8674(85)90170-9. - DOI - PubMed

Publication types