General Information of the m6A Target Gene (ID: M6ATAR00640)
Target Name Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)
Synonyms
Deubiquitinating enzyme CYLD; Ubiquitin thioesterase CYLD; Ubiquitin-specific-processing protease CYLD
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Gene Name CYLD
Chromosomal Location 16q12.1
Family Peptidase C19 family
Function
Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis. Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation. Negative regulator of Wnt signaling . Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis. Required for normal cell cycle progress and normal cytokinesis . Inhibits nuclear translocation of NF-kappa-B. Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation. Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (By similarity). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (By similarity). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (By similarity). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins. Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (By similarity). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (By similarity). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades.
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Gene ID 1540
Uniprot ID
CYLD_HUMAN
HGNC ID
HGNC:2584
Ensembl Gene ID
ENSG00000083799
KEGG ID
hsa:1540
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CYLD can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
YTH domain-containing protein 2 (YTHDC2) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, YTHDC2 functions as a tumor suppressor through the Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)/NF-Kappa-B signaling pathway, which is mediated by m6A modification.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model Approximately 5×106 normal H1299 cells or stable YTHDC2-overexpressing H1299 cells were implanted subcutaneously into the right flank of the animals (n=8 mice per group). Animals were euthanized by cervical dislocation ~30 days after implantation, and tumors were collected and photographed.
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, YTHDC2 functions as a tumor suppressor through the Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)/NF-Kappa-B signaling pathway, which is mediated by m6A modification.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
Target Regulation Up regulation
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model Approximately 5×106 normal H1299 cells or stable YTHDC2-overexpressing H1299 cells were implanted subcutaneously into the right flank of the animals (n=8 mice per group). Animals were euthanized by cervical dislocation ~30 days after implantation, and tumors were collected and photographed.
References
Ref 1 Downregulation of m(6)A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-KappaB Pathway. Int J Biol Sci. 2021 Jun 22;17(10):2633-2651. doi: 10.7150/ijbs.58514. eCollection 2021.