Cited by 378Telomeres, Telomerase, and SenescenceNF-κB Signaling PathwaysTGF-β signaling in diseases

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Telomerase directly regulates NF-κB-dependent transcription

Ghosh, Arkasubhra, Saginc, Gaye, Leow, Shi Chi, Khattar, Ekta, Shin, Eun Myong, Yan, Ting Dong, Wong, Marc, Zhang, Zhizhuo, Li, Guoliang, Sung, Wing-Kin, Zhou, Jianbiao, Chng, Wee Joo, Li, Shang, Liu, Edison, Tergaonkar, Vinay·2012·Nature Cell Biology

DOI 10.1038/ncb2621

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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.

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Authors: Ghosh, A., Saginc, G., Leow, S. C., Khattar, E., Shin, E. M., Yan, T. D., Wong, M., Zhang, Z., Li, G., Sung, W.-K., Zhou, J., Chng, W. J., Li, S., Liu, E., & Tergaonkar, V.
Affiliations: Institute of Molecular and Cell Biology (SG)
Genome Institute of Singapore (SG)
National University of Singapore (SG)
Cancer Science Institute of Singapore (SG)
Corresponding author: Tergaonkar, Vinay
ORCID: Ghosh, Arkasubhra
Saginc, Gaye
Khattar, Ekta
Zhang, Zhizhuo
Li, Guoliang
Sung, Wing-Kin
Zhou, Jianbiao
Chng, Wee Joo
Li, Shang
Tergaonkar, Vinay
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2012-11-18
Volume: 14
Issue: 12
Pages: 1270-1281
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb2621
OpenAlex: W2033861401
Cited by: 378
References: 70
Citations by year: 2026: 20 · 2025: 27 · 2024: 27 · 2023: 34 · 2022: 29 · 2021: 30 · 2020: 32 · 2019: 22 · 2018: 28 · 2017: 19 · 2016: 33 · 2015: 48 · 2014: 15 · 2013: 14
FWCI: 16.73
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Cell Biology (publishedVersion)
PubMed (publishedVersion)
National University of Singapore (submittedVersion)
Funders: Agency for Science, Technology and Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: telomerase, NF-κB, NF-κB p65, transcriptional regulation, telomere elongation, chronic inflammation, tumor progression, interleukin-6, TNF-α, feedforward control, telomerase reactivation, tumor inflammation
MeSH terms: Animals, Female, Humans, Male, Promoter Regions, Genetic, Transcription, Genetic, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, NF-kappa B, Telomerase, Cell Line, Tumor, Mice

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Telomerase directly regulates NF-κB-dependent transcription

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