CYLD (gene)

The CYLD lysine 63 deubiquitinase gene, also termed the CYLD gene,^[5] CYLD is an evolutionary ancient gene found to be present as far back on the evolutionary scale as in sponges.^[6] In humans, this gene is located in band 12.1 on the long (or "q") arm of chromosome 16^[7] and is known to code (i.e. direct the production of) multiple proteins through the process of alternative splicing.^[8]

The CYLD gene in known to code for a cytoplasmic protein, termed CYLD lysine 63 deubiquitinase (here termed CYLD protein), which has three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains (areas or the protein controlling critical functions^[9]). CYLD protein is a deubiquitinating enzyme, i.e. a protease that removes ubiquitin from certain proteins and thereby regulates these proteins' activities. CYLD protein removes ubiquitin from proteins involved in regulating the NF-κB, Wnt, notch, TGF-β,^[10] and JNK^[11] cell signaling pathways; these pathways normally act to regulate hair formation, cell growth, cell survival, inflammatory responses, and/or tumor development.^[10][11]

The CYLD gene is classified as a tumor suppressor gene, i.e. a gene that regulates cell growth and when inactivated by a mutation leads to uncontrolled cell growth and the formation of tumors.^[12] Inactivating mutations in this gene occur in essentially all cases of the CYLD cutaneous syndrome, a hereditary disorder in which individuals develop multiple skin tumors. The CYLD cutaneous syndrome includes three somewhat different forms of the disease: the multiple familial trichoepithelioma-type, Brooke–Spiegler syndrome-type, and familial cylindromatosis-type.^[10] CYLD gene mutations are also associated with T-Cell Acute Lymphoblastic Leukemia,^[12] multiple myeloma, hepatocellular carcinoma, neuroblastoma, pancreatic cancer,^[13] uterine cancer, stomach cancer, colon cancer, lung cancer, and human papillomavirus-associated cancers.^[11]