Cyld
Synonym(s)
DefinitionThis section has been translated automatically.
CYLD is the acronym for "Cylindroma gene", a gene located on chromosome 16q12-q13, which was first discovered as a tumour suppressor gene. Its mutation is associated with various (benign) tumour types, such as autosomal-dominantly inherited cylindromes and multiple familial trichoepitheliomas.
The CYLD gene encodes a desubiquitinating enzyme, a deubiquitinase, which specifically cleaves 'Lys-63' and linear 'Met-1' linked polyubiquitin chains. The ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis, thereby establishing its tumour suppressor function. The enzyme thus acts as a regulator for various cellular processes such as the regulation of microtubule dynamics, cell proliferation, apoptosis, cell polarization, cell migration and angiogenesis. CYLD plays a role in the regulation of inflammation and the innate immune response via its effects on the activation of NF-KappaB.
The process of proteinubiquitination itself is a reversible reaction in which ubiquitin chains of a protein are deconjugated by specific deubiquitinases (= DUBs).
CYLD also supports STING signal transduction by stabilizing the STING protein (Zhang L et al. 2018). In addition, sCYLD regulates further signalling cascades such as the NFkB signalling pathway and the mitogen-activated protein kinase through its catalytic activity (Trompouki E et al. 2003).
General informationThis section has been translated automatically.
Alternative splice forms of CYLD influence transcription factors and inflammatory processes. For example, sCYLD mediates the ubiquitination of SMAD7 and thus inhibits the TGF-beta signalling pathway. This inhibition leads to a promotion of inflammatory reactions, e.g. in inflammatory bowel diseases such as Crohn's disease.
LiteratureThis section has been translated automatically.
- Biggs PJ et al (1995) Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: evidence for its role as a tumour suppressor gene". Nature Genetics 11: 441-443
- Mathis BJ et al (2015) CYLD-mediated signaling and diseases. Curr drug targets 16: 284-94
- Trompouki E et al (2003) CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature 424: 793-796
- Zhang L et al (2018) The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway. PLoS pathogens 14: e1007435