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Tumour suppressors

Cylindromatosis: cause and treatment

Nature Reviews Cancer volume 3, pages 716–717 (2003)Cite this article

Cylindromatosis is a rare tumour of the skin appendages, and is caused by mutation of the tumour suppressor CYLD ; however, the function of this gene has only recently been determined. Three papers, published in Nature, now report that CYLD is a de-ubiquitylating enzyme that negatively regulates NF-κB activity.

By contrast, Brummelkamp et al. performed an RNA interference (RNAi) screen to knockdown expression of putative de-ubiquitylating enzymes and found that loss of CYLD resulted in increased expression from an NF-κB luciferase reporter construct. The same knockdown in cells resulted in an enhanced response to TNF-induced stimulation of IKKβ activity, and a subsequent decrease in IκBα levels. Both Trompouki et al. and Kovalenko et al. further analysed the link between CYLD and the NF-κB pathway. Trompouki et al. found that wild-type CYLD, but not CYLD mutants, prevented TNF receptors from activating NF-κB, and that RNAi to knockdown CYLD enhanced the activation of NF-κB in response to the CD40 ligand. Kovalenko et al. showed that overexpressing CYLD, but not catalytically inactive CYLD, inhibited the induction of NF-κB by the TNF and IL-1 ligands.

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References

ORIGINAL RESEARCH PAPER

  1. Trompouki, E. et al. CYLD is a deubiquitinating enyme that negatively regulates NF-κB activation by TNFR family members. Nature 424, 793–796 (2003)

    Article  CAS  Google Scholar 

  2. Brummelkamp, T. R. et al. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB. Nature 424, 797–801 (2003)

    Article  CAS  Google Scholar 

  3. Kovalenko, A. et al. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature 424, 801–805 (2003)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Wilkinson, K. D. Aspirin, ubiquitin and cancer. Nature 424, 738–739 (2003)

    Article  CAS  Google Scholar 

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Authors
  1. Emma Greenwood
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Greenwood, E. Cylindromatosis: cause and treatment. Nat Rev Cancer 3, 716–717 (2003). https://doi.org/10.1038/nrc1202

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  • DOI: https://doi.org/10.1038/nrc1202

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