Article | Published:

Telomerase directly regulates NF-κB-dependent transcription

Nature Cell Biology volume 14, pages 12701281 (2012) | Download Citation

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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Acknowledgements

We thank the Agency for Science Technology and Research, Singapore (A*Star) for funding and support to the V.T. laboratory.

Author information

Affiliations

  1. Laboratory of NFκB Signaling, IMCB, Proteos, 138673, Singapore

    • Arkasubhra Ghosh
    • , Shi Chi Leow
    • , Ekta Khattar
    • , Eun Myong Shin
    • , Marc Wong
    •  & Vinay Tergaonkar
  2. Cancer Biology and Pharmacology, Genome Institute of Singapore, 138672, Singapore

    • Gaye Saginc
    •  & Edison Liu
  3. Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 169857, Singapore

    • Ting Dong Yan
    •  & Shang Li
  4. School of Computing, National University of Singapore, 119077, Singapore

    • Zhizhuo Zhang
    •  & Wing-Kin Sung
  5. Computational and Systems Biology, Genome Institute of Singapore, 138672, Singapore

    • Guoliang Li
    •  & Wing-Kin Sung
  6. Cancer Science Institute of Singapore, 119074, Singapore

    • Jianbiao Zhou
    •  & Wee Joo Chng

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Contributions

A.G., S.C.L., S.L., E.L. and V.T. designed experiments and planned the project. G.S., Z.Z., G.L. and W-K.S. carried our genome-wide analyses and were guided by E.L. A.G., E.M.S., E.K., S.C.L., M.W. and T.D.Y. carried out all experiments and animal work. J.Z. and W.J.C. provided patient samples and carried out experiments with patient material. A.G. and V.T. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Vinay Tergaonkar.

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https://doi.org/10.1038/ncb2621

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