title: Reactivation of telomerase in cancer.
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.
authors: Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Proteos, 61, Biopolis Drive, Singapore, 138673, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117597, Singapore.
authors: Semih Can
authors: SC
authors: Akincilar
authors: Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Proteos, 61, Biopolis Drive, Singapore, 138673, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117597, Singapore.
authors: Bilal
authors: B
authors: Unal
authors: Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Proteos, 61, Biopolis Drive, Singapore, 138673, Singapore. vinayt@imcb.a-star.edu.sg.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, 117597, Singapore. vinayt@imcb.a-star.edu.sg.|Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia. vinayt@imcb.a-star.edu.sg.
authors: Vinay
authors: V
authors: Tergaonkar
mesh_terms: D004789:Enzyme Activation / Q000502:physiology; D044127:Epigenesis, Genetic; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Cancer; NF-κB; TERT reactivation; Tert promoter mutation; Transcription