{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:45:02Z","timestamp":1779331502384,"version":"3.51.4"},"reference-count":106,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,13]],"date-time":"2016-01-13T00:00:00Z","timestamp":1452643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cylindromatosis (CYLD) is a deubiquitination enzyme involved in the regulation of different cellular processes including inflammation, fibrosis, and cancer. The function of CYLD is via deubiquitination of specific substrates in different signaling pathways including NF\u2010\u03baB, Notch, and JNK. CYLD contributes to hepatic homeostasis and restoration upon liver injury. Mutation or disruption of the activity of CYLD in animals aggravates acute as well as chronic liver injury and promotes development and progression of hepatocellular cancer. This is mediated by a shift of the balance toward pro\u2010inflammatory, pro\u2010fibrogenic, and pro\u2010oncogenic pathways. In this review, we will explain the liver\u2010associated signaling pathways that CYLD regulates in hepatocytes and nonparenchymal liver cells under physiological and pathological conditions. We will also describe the most recent findings concerning CYLD\u2010mediated downstream signaling in the liver in situations such as injury, infection, inflammation, and cancer. Furthermore, we will discuss the potential of novel diagnostic tools and treatment strategies utilizing CYLD and its target genes.<\/jats:p>","DOI":"10.1002\/med.21381","type":"journal-article","created":{"date-parts":[[2016,1,14]],"date-time":"2016-01-14T09:02:58Z","timestamp":1452762178000},"page":"342-359","source":"Crossref","is-referenced-by-count":24,"title":["Cylindromatosis\u2014A Protective Molecule against Liver Diseases"],"prefix":"10.1002","volume":"36","author":[{"given":"Claus","family":"Hellerbrand","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital Regensburg  93053 Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramin","family":"Massoumi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medicon Village Lund University  22381 Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e3283521d82"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3269"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0145-y"},{"key":"e_1_2_12_7_1","article-title":"Heterogeneity of liver cancer and personalized therapy","author":"Li L","year":"2015","journal-title":"Cancer Lett"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i36.10262"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2013.183"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.503"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/35056563"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.589"},{"issue":"6","key":"e_1_2_12_13_1","first-page":"536","article-title":"Atypical ubiquitin chains: New molecular signals","volume":"9","author":"Ikeda F","year":"2008","journal-title":"Protein Modifications: Beyond the Usual Suspects\u2019 Review Series. EMBO Reports"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8090-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3394"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1225"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2673"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-136259"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-051013-022958"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2780"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.082307.091526"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.10.003"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080798"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.243"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27682"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26954"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0398-6_8"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/76006"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2004.07.012"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708470200"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.317"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2723"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.81424"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.12.018"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.02.007"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/614097"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.10.187"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450115666141024152421"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2337"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7465-4"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01803"},{"issue":"6950","key":"e_1_2_12_42_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nature01802","article-title":"The tumour suppressor CYLD negatively regulates NF\u2010kappa B signalling by deubiquitination","volume":"424","author":"Kovalenko A","year":"2003","journal-title":"Nature"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01811"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.041"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5585"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.136"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.27838"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319341111"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201103-025SD"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27209"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt335"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.04.026"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i45.17049"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00061.2009"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01811"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2362"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-008-8091-0"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.033"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124958"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260111"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/5593"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02820"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21604"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3572006re13"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31325-0"},{"issue":"118","key":"e_1_2_12_66_1","first-page":"1921","article-title":"Roles of hepatic progenitor cells activation, ductular reaction proliferation and Notch signaling in morbid obesity","volume":"59","author":"Liew PL","year":"2012","journal-title":"Hepato\u2010gastroenterology"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.08.006"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.7.15067"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2573"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27394"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003455"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445116"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.008"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306842"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1776"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.09.119"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.04.012"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.100"},{"issue":"9","key":"e_1_2_12_80_1","first-page":"4253","article-title":"Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse","volume":"43","author":"Vesselinovitch SD","year":"1983","journal-title":"Cancer Res"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl081"},{"key":"e_1_2_12_82_1","first-page":"185","article-title":"NF\u2010kappaB in liver cancer: The plot thickens","volume":"349","author":"Finkin S","year":"2011","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.6.2662"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0909-8"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.10.041"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep09993"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-015-2455-6"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyv063"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.03.058"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.134"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.76"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-248526"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b15-00325"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2018"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2297-0_8"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110591"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e3280109424"},{"issue":"7","key":"e_1_2_12_98_1","first-page":"1180","article-title":"Therapeutically targeting microRNAs in liver cancer","volume":"19","author":"Drakaki A","year":"2013","journal-title":"Curr Pharm Des"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.13"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082044"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019613"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3181af5e35"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.9.1.143"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4398"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.03.032"},{"key":"e_1_2_12_106_1","article-title":"The ubiquitin\u2010proteasome system and its potential application in hepatocellular carcinoma therapy","author":"Chen YJ","year":"2015","journal-title":"Cancer Lett."},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1656-6"}],"container-title":["Medicinal Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmed.21381","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmed.21381","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.21381","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T01:10:39Z","timestamp":1696381839000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/med.21381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,13]]},"references-count":106,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/med.21381"],"URL":"https:\/\/doi.org\/10.1002\/med.21381","archive":["Portico"],"relation":{},"ISSN":["0198-6325","1098-1128"],"issn-type":[{"value":"0198-6325","type":"print"},{"value":"1098-1128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,13]]}}}