CYLD : CYLD lysine 63 deubiquitinase

Description

The CYLD (CYLD lysine 63 deubiquitinase) is a protein-coding gene located on chromosome 16.

The CYLD gene provides instructions for making an enzyme that helps regulate numerous signaling pathways, many of which are involved in cell growth. These pathways include nuclear factor-kappa-B(NF-KB), Wnt, c-Jun N-terminal kinase (JNK), transforming growth factor beta-1 (TGFB1), and Notch signaling pathways. By regulating these signaling pathways, the CYLD enzyme helps cells respond properly to signals that promote cell growth and division (proliferation) or self-destruction (apoptosis), as necessary. By regulating signals that control cell growth, the CYLD enzyme acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.

CYLD is a deubiquitinase that specifically removes 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains. This enzyme plays a key role in regulating various cellular processes, including NF-kappa-B activation, TNF-alpha-induced necroptosis, and cell survival, proliferation, and differentiation. CYLD negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors. It also acts as a negative regulator of Wnt signaling. CYLD inhibits HDAC6, leading to increased acetylation of alpha-tubulin and stabilization of microtubules. This enzyme is important for normal cell cycle progression and cytokinesis. It also regulates inflammation and innate immune responses by influencing NF-kappa-B activation. While CYLD is not essential for the maturation of intrathymic natural killer cells, it is required for the survival of immature NK cells. CYLD negatively regulates TNFRSF11A signaling and osteoclastogenesis. It is involved in ciliogenesis by facilitating the migration and docking of ciliary basal bodies to the plasma membrane. The ability of CYLD to remove linear polyubiquitin chains is crucial for innate immunity and TNF-alpha-induced necroptosis. CYLD is recruited to the LUBAC complex through its interaction with SPATA2, preventing the formation of linear polyubiquitin chains on target proteins. CYLD regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation. It also participates in TNF-alpha-induced necroptosis by removing linear polyubiquitin chains from RIPK1, modulating the kinase activity of RIPK1. CYLD negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chains from NLRP6, reducing the interaction between NLRP6 and PYCARD/ASC and inhibiting the formation of the NLRP6 inflammasome. CYLD removes 'Lys-63' linked polyubiquitin chains from MAP3K7, inhibiting phosphorylation and blocking downstream activation of the JNK-p38 kinase cascades. CYLD also removes 'Lys-63'-linked polyubiquitin chains from MAP3K1 and MAP3K3, preventing their interaction with MAP2K1 and MAP2K2.

CYLD is also known as BRSS, CDMT, CYLD1, CYLDI, EAC, FTDALS8, MFT, MFT1, SBS, TEM, USPL2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing