title: Telomerase directly regulates NF-κB-dependent transcription.
abstract: Although elongation of telomeres is thought to be the prime function of reactivated telomerase in cancers, this activity alone does not account for all of the properties that telomerase reactivation attributes to human cancer cells. Here, we uncover a link between telomerase and NF-κB, a master regulator of inflammation. We observe that while blocking NF-κB signalling can inhibit effects of telomerase overexpression on processes relevant to transformation, increasing NF-κB activity can functionally substitute for reduced telomerase activity. Telomerase directly regulates NF-κB-dependent gene expression by binding to the NF-κB p65 subunit and recruitment to a subset of NF-κB promoters such as those of IL-6 and TNF-α, cytokines that are critical for inflammation and cancer progression. As NF-κB can transcriptionally upregulate telomerase levels, our findings suggest that a feed-forward regulation between them could be the key mechanistic basis for the coexistence of chronic inflammation and sustained telomerase activity in human cancers.
authors.affiliation: Laboratory of NFκB Signaling, IMCB, Proteos, 138673, Singapore.
authors.forename: Arkasubhra
authors.initials: A
authors.lastname: Ghosh
authors.forename: Gaye
authors.initials: G
authors.lastname: Saginc
authors.forename: Shi Chi
authors.initials: SC
authors.lastname: Leow
authors.forename: Ekta
authors.initials: E
authors.lastname: Khattar
authors.forename: Eun Myong
authors.initials: EM
authors.lastname: Shin
authors.forename: Ting Dong
authors.initials: TD
authors.lastname: Yan
authors.forename: Marc
authors.initials: M
authors.lastname: Wong
authors.forename: Zhizhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Edison
authors.initials: E
authors.lastname: Liu
authors.forename: Vinay
authors.initials: V
authors.lastname: Tergaonkar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019098:Telomerase