CYLD lysine 63 deubiquitinase (CYLD)

CYLD lysine 63 deubiquitinase (CYLD) is a cytoplasmic deubiquitinating enzyme that specifically cleaves K63-linked polyubiquitin chains from substrate proteins[5]. It is a member of the ubiquitin-specific protease family (USP) and contains an N-terminal region with three CAP-Gly domains (involved in microtubule binding) and a C-terminal USP catalytic domain[2][6]. CYLD acts as a tumor suppressor, with its most studied role being the negative regulation of the NF-κB signaling pathway through the removal of K63-linked ubiquitin chains from proteins such as NEMO (IKKγ), TRAF2, TRAF6, TAK1, and RIPK1, thus restraining inflammatory and survival signaling[1][2][6]. Beyond NF-κB, CYLD participates in the regulation of Wnt, TGF-β, JNK, p53, cell cycle progression, autophagy, and cytoskeletal dynamics[6][1]. Genetic inactivation of CYLD causes familial skin tumors (CYLD cutaneous syndrome) and is implicated in a variety of cancers, as well as inflammatory and infectious diseases[3][1]. No clinically approved direct CYLD-targeting drugs are currently available.

Other names

Ubiquitin carboxyl-terminal hydrolase CYLDDeubiquitinating enzyme CYLDUbiquitin thioesterase CYLDUbiquitin-specific-processing protease CYLDCYLD1KIAA0849HSPC057USPL2BRSSCDMTEACFTDALS8MFTMFT1SBSTEM

Not applicable (no specific drugs), but inhibitors or activators would impact K63-linked deubiquitination of signaling proteins such as NEMO, TRAF2, TRAF6, TAK1, RIPK1, affecting pathways like NF-κB, Wnt, TGF-β, JNK[1][2][6].