CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members
Eirini Trompouki,
Eudoxia Hatzivassiliou,
Theodore Tsichritzis,
Hannah Farmer,
Alan Ashworth and
George Mosialos ()
Additional contact information
Eirini Trompouki: Biomedical Sciences Research Center ‘Alexander Fleming’
Eudoxia Hatzivassiliou: Biomedical Sciences Research Center ‘Alexander Fleming’
Theodore Tsichritzis: Biomedical Sciences Research Center ‘Alexander Fleming’
Hannah Farmer: Institute of Cancer Research, Chester Beatty Laboratories
Alan Ashworth: Institute of Cancer Research, Chester Beatty Laboratories
George Mosialos: Biomedical Sciences Research Center ‘Alexander Fleming’
Nature, 2003, vol. 424, issue 6950, 793-796
Abstract:
Abstract Familial cylindromatosis is an autosomal dominant predisposition to tumours of skin appendages called cylindromas. Familial cylindromatosis is caused by mutations in a gene encoding the CYLD protein of previously unknown function1. Here we show that CYLD is a deubiquitinating enzyme that negatively regulates activation of the transcription factor NF-κB by specific tumour-necrosis factor receptors (TNFRs). Loss of the deubiquitinating activity of CYLD correlates with tumorigenesis. CYLD inhibits activation of NF-κB by the TNFR family members CD40, XEDAR and EDAR in a manner that depends on the deubiquitinating activity of CYLD. Downregulation of CYLD by RNA-mediated interference augments both basal and CD40-mediated activation of NF-κB. The inhibition of NF-κB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2) and, to a lesser extent, TRAF6. These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-κB that is required for appropriate cellular homeostasis of skin appendages.
Date: 2003
References: Add references at CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/nature01803 Abstract (text/html)
Access to the full text of the articles in this series is restricted.
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:424:y:2003:i:6950:d:10.1038_nature01803
Ordering information: This journal article can be ordered from
https://www.nature.com/
DOI: 10.1038/nature01803
Access Statistics for this article
Nature is currently edited by Magdalena Skipper
More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().