CYLD
CYLD (CYLD lysine 63 deubiquitinase, also known as KIAA0849, USPL2 or CYLD1) is a cytoplasmic deubiquitinating enzyme that cleaves 'Lys-63'-linked and linear 'Met-1'-linked polyubiquitin chains. It restrains NF-kappa-B signalling and contributes to necroptosis, cell cycle progression and ciliogenesis. Browse Assay Genie's current range of CYLD research reagents below, or read on for the biology behind the target.
CYLD is a deubiquitinase that specifically removes 'Lys-63'-linked and linear 'Met-1'-linked polyubiquitin chains from its substrates. By trimming these chains from upstream signalling factors, it acts as a negative regulator of NF-kappa-B activation and inhibits nuclear translocation of NF-kappa-B. Through this route it helps regulate cell survival, proliferation, differentiation, inflammation and the innate immune response. CYLD removes 'Lys-63' chains from MAP3K7, which blocks downstream activation of the JNK-p38 kinase cascades, and from MAP3K1 and MAP3K3, which affects their interaction with MAP2K1 and MAP2K2. It also acts as a negative regulator of Wnt signalling.
CYLD is recruited to the LUBAC complex through SPATA2, where it restricts linear polyubiquitin formation. It does this on RIPK2 after NOD2 stimulation, and on RIPK1 during TNF-induced necroptosis, where it regulates RIPK1 kinase activity. It also removes 'Lys-63' chains from NLRP6, which reduces inflammasome formation and limits intestinal inflammation. CYLD does not act on heterotypic 'Lys-63'/'Lys-48' branched chains. Beyond NF-kappa-B, it inhibits HDAC6, which promotes alpha-tubulin acetylation and microtubule stabilisation. This supports cell polarisation, migration, angiogenesis, normal cytokinesis and cell cycle progress. It also lets ciliary basal bodies migrate and dock at the plasma membrane, independently of NF-kappa-B. It negatively regulates TNFRSF11A signalling and osteoclastogenesis, and is needed for the survival of immature natural killer cells.
The CYLD gene encodes a cytoplasmic protein with three CAP-GLY domains and belongs to the peptidase C19 family. Its HGNC name derives from the earlier designation cylindromatosis (turban tumour syndrome). Mutations are associated with cylindromatosis, multiple familial trichoepithelioma and Brooke-Spiegler syndrome. Alternative splice variants encoding different isoforms have been described. Mouse and rat both carry a Cyld ortholog.
CYLD removes ubiquitin chains from upstream factors to limit NF-kappa-B activation, making it central to studies of survival, proliferation and inflammation.
By editing linear ubiquitin on RIPK1 and RIPK2 within LUBAC-linked complexes, CYLD shapes TNF-induced necroptosis and NOD2 responses.
CYLD inhibits HDAC6, stabilises microtubules and enables basal body docking, linking it to cytokinesis, migration and cilium formation.
Mutations in the CYLD gene are associated with cylindromatosis, multiple familial trichoepithelioma and Brooke-Spiegler syndrome.
CYLD is a deubiquitinase that cleaves 'Lys-63'-linked and linear 'Met-1'-linked polyubiquitin chains. It negatively regulates NF-kappa-B activation, and also acts on Wnt signalling, TNF-induced necroptosis, microtubule dynamics, cytokinesis and ciliogenesis. Check the datasheet of any product for its validated reactivity.
Aliases and previous symbols include KIAA0849, USPL2 and CYLD1. The earlier gene name was cylindromatosis (turban tumour syndrome). The UniProt protein name is ubiquitin carboxyl-terminal hydrolase CYLD. NCBI reports alternative splice variants that encode different isoforms.
Mutations in the CYLD gene are associated with cylindromatosis, multiple familial trichoepithelioma and Brooke-Spiegler syndrome. Mouse and rat each have a Cyld ortholog. Check the datasheet of any product for its validated reactivity.
Other ubiquitin pathway enzymes, NF-kappa-B and necroptosis signalling partners, and microtubule regulators with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NQC7; product specifications from Assay Genie datasheets.