Cyld

Summary

Gene Symbol: Cyld
Description: CYLD lysine 63 deubiquitinase
Alias: 2010013M14Rik, 2900009M21Rik, C130039D01Rik, CDMT, CYLD1, EAC, mKIAA0849, ubiquitin carboxyl-terminal hydrolase CYLD, cylindromatosis (turban tumor syndrome), deubiquitinating enzyme CYLD, ubiquitin thioesterase CYLD, ubiquitin thiolesterase CYLD, ubiquitin-specific-processing protease CYLD
Species: mouse

Top Publications

  1. ncbi Regulation of T cell development by the deubiquitinating enzyme CYLD
    William W Reiley
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Nat Immunol 7:411-7. 2006
  2. doi CYLD controls c-MYC expression through the JNK-dependent signaling pathway in hepatocellular carcinoma
    Rajeswara Rao Pannem
    Department of Laboratory Medicine, Skane University Hospital, Lund University, Malmö SE 20502, Sweden
    Carcinogenesis 35:461-8. 2014
  3. pmc CYLD negatively regulates transforming growth factor-β-signalling via deubiquitinating Akt
    Jae Hyang Lim
    Center for Inflammation, Immunity and Infection and Department of Biology, Georgia State University, Atlanta, 30303, USA
    Nat Commun 3:771. 2012
  4. pmc The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation
    Neesar Ahmed
    Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA
    Nat Immunol 12:1176-83. 2011
  5. pmc Caspase 8 inhibits programmed necrosis by processing CYLD
    Marie Anne O'Donnell
    Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Cell Biol 13:1437-42. 2011
  6. doi The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation
    Marion C Bonnet
    Institute for Genetics, Center for Molecular Medicine, and Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Immunity 35:572-82. 2011
  7. doi FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
    Patrick Simon Welz
    Institute for Genetics, Centre for Molecular Medicine, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Nature 477:330-4. 2011
  8. pmc cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Technologiepark 927, Zwijnaarde Ghent 9052, Belgium
    Cell Death Differ 18:656-65. 2011
  9. doi Thymocyte-specific truncation of the deubiquitinating domain of CYLD impairs positive selection in a NF-kappaB essential modulator-dependent manner
    Ageliki Tsagaratou
    School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
    J Immunol 185:2032-43. 2010
  10. pmc CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling
    Andrew Joon Lee
    Department of Immunology, The University of Texas MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
    J Biol Chem 285:15696-703. 2010

Scientific Experts

  • Matthias Bros
  • Lluis Espinosa
  • Marie Anne O'Donnell
  • Marie W Wooten
  • Ramin Massoumi
  • Jae Hyang Lim
  • Shao Cong Sun
  • Ageliki Tsagaratou
  • Minying Zhang
  • Jian dong Li
  • Haidong Xu
  • George Mosialos
  • Wei Jin
  • Yongge Zhao
  • Hirofumi Jono
  • Andrew J Lee
  • Tomoaki Koga
  • Ari Waisman
  • Ato Wright
  • Nadine Hövelmeyer
  • Sonja Reissig
  • Xuefeng Wu
  • Manolis Pasparakis
  • Ashish Jain
  • Dimitris L Kontoyiannis
  • William W Reiley
  • Chang Hoon Woo
  • Andrew Joon Lee
  • Katharina Wex
  • Mikyoung Chang
  • Eirini Trompouki
  • Gopala Nishanth
  • Un Hwan Ha
  • Marion C Bonnet
  • Geert Van Loo
  • Yuxian Huang
  • Wenhong Zhang
  • Patrick Simon Welz
  • Chi A Ma
  • Chen Yan
  • Patricia Bourne
  • Haodong Xu
  • Reinhard Fassler
  • Akhee S Jahan
  • Hajime Ishinaga
  • Diana Legarda
  • Demetrios N Karatzas
  • Fei He
  • Yilang Tang
  • Melania Tesio
  • Hui Wang
  • Rajeswara R Pannem
  • Yunfan Yang
  • Kim Newton
  • Wenzhuo Y Wang
  • Thibaut Eguether
  • Michael Naumann
  • Rajeswara Rao Pannem
  • Christoph Dorn
  • Stephen A Schworer
  • Claus Hellerbrand
  • Dirk Schluter
  • Xing Li Wang
  • Dongqi Tang
  • Taixing Cui
  • Wenjuan Wang
  • Siying Li
  • Kensei Komatsu
  • David M Moquin
  • Masanori Miyata
  • Hengwei Zhang
  • Xing Liu
  • Josefa P Alameda
  • Nikolaus Thuille
  • Maria A Ermolaeva
  • Kristofer Ahlqvist
  • Shuai Liu
  • Kostas Nikolaou
  • Yuanyuan Chu
  • Kumaran Sundaram
  • Teresa D'Altri
  • Neesar Ahmed
  • Paula Miliani de Marval
  • N Vanlangenakker
  • Gang Liang
  • Sofia Grammenoudi
  • Xiaofei Zhou
  • JiHoon Chang
  • Xiangbin Xu
  • Sara A Wickström

Detail Information

Publications67

  1. ncbi Regulation of T cell development by the deubiquitinating enzyme CYLD
    William W Reiley
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    Nat Immunol 7:411-7. 2006
    ..Here we identify the deubiquitinating enzyme CYLD as a positive regulator of proximal T cell receptor signaling in thymocytes...
  2. doi CYLD controls c-MYC expression through the JNK-dependent signaling pathway in hepatocellular carcinoma
    Rajeswara Rao Pannem
    Department of Laboratory Medicine, Skane University Hospital, Lund University, Malmö SE 20502, Sweden
    Carcinogenesis 35:461-8. 2014
    ..Cylindromatosis (CYLD), a deubiquitination enzyme, is able to cleave the polyubiquitin chains from the substrate and to regulate ..
  3. pmc CYLD negatively regulates transforming growth factor-β-signalling via deubiquitinating Akt
    Jae Hyang Lim
    Center for Inflammation, Immunity and Infection and Department of Biology, Georgia State University, Atlanta, 30303, USA
    Nat Commun 3:771. 2012
    ..Here we show that loss of deubiquitinase CYLD led to the development of lung fibrosis in mice after infection with Streptococcus pneumoniae...
  4. pmc The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation
    Neesar Ahmed
    Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA
    Nat Immunol 12:1176-83. 2011
    ..Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs...
  5. pmc Caspase 8 inhibits programmed necrosis by processing CYLD
    Marie Anne O'Donnell
    Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Cell Biol 13:1437-42. 2011
    ..We now identify CYLD as a substrate for caspase 8 that satisfies these criteria...
  6. doi The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation
    Marion C Bonnet
    Institute for Genetics, Center for Molecular Medicine, and Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Immunity 35:572-82. 2011
    ..necrosis (termed necroptosis) of FADD-deficient keratinocytes, which was partly dependent on the deubiquitinating enzyme CYLD and tumor necrosis factor (TNF)-TNF receptor 1 signaling...
  7. doi FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
    Patrick Simon Welz
    Institute for Genetics, Centre for Molecular Medicine, University of Cologne, Zülpicher Str 47a, 50674 Cologne, Germany
    Nature 477:330-4. 2011
    ..Epithelial-specific inhibition of CYLD, a deubiquitinase that regulates cellular necrosis, prevented colitis development in FADD(IEC-KO) but not in NEMO(..
  8. pmc cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Technologiepark 927, Zwijnaarde Ghent 9052, Belgium
    Cell Death Differ 18:656-65. 2011
    ..1 (TAK1) which prevents it from activating caspase-8-dependent death, a process reverted by the de-ubiquitinase CYLD. RIP1 is also a regulator of necrosis, a caspase-independent type of cell death...
  9. doi Thymocyte-specific truncation of the deubiquitinating domain of CYLD impairs positive selection in a NF-kappaB essential modulator-dependent manner
    Ageliki Tsagaratou
    School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
    J Immunol 185:2032-43. 2010
    The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function...
  10. pmc CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling
    Andrew Joon Lee
    Department of Immunology, The University of Texas MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
    J Biol Chem 285:15696-703. 2010
    T cell receptor-stimulated NF-kappaB activation requires CARMA1 and is negatively regulated by the deubiquitinase CYLD. Recent studies suggest that CARMA1 regulates regulatory T cell (Treg) development, although the role of NF-kappaB in ..
  11. pmc CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin
    Sara A Wickström
    Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany
    EMBO J 29:131-44. 2010
    b>CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis...
  12. pmc Truncation of the catalytic domain of the cylindromatosis tumor suppressor impairs lung maturation
    Eirini Trompouki
    Institute of Immunology, Biomedical Sciences Research Center Al Fleming, 34 Al Fleming Str, Vari 16672, Greece
    Neoplasia 11:469-76. 2009
    b>Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways...
  13. doi CYLD is a crucial negative regulator of innate immune response in Escherichia coli pneumonia
    Jae Hyang Lim
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Cell Microbiol 10:2247-56. 2008
    ..The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB...
  14. pmc Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD
    Minying Zhang
    Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 283:18621-6. 2008
    ..However, how these kinases are negatively regulated remains unclear. We show here that the tumor suppressor CYLD has an essential role in preventing aberrant activation of IKKepsilon/TBK1...
  15. ncbi Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections
    Jae Hyang Lim
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Immunity 27:349-60. 2007
    ..Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-kappaB transcription factor signaling, ..
  16. ncbi Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling
    Ramin Massoumi
    Department of Molecular Medicine, Max Planck Institute of Biochemistry, D 82152 Martinsried, Germany
    Cell 125:665-77. 2006
    Mutations in the CYLD gene cause tumors of hair-follicle keratinocytes. The CYLD gene encodes a deubiquitinase that removes lysine 63-linked ubiquitin chains from TRAF2 and inhibits p65/p50 NF-kappaB activation...
  17. pmc Impaired regulation of NF-kappaB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice
    Jun Zhang
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 116:3042-9. 2006
    Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors. However, the regulatory function of CYLD remains unsettled...
  18. ncbi Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells
    Wei Jin
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 282:15884-93. 2007
    ..Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells...
  19. ncbi NF-kappaB is essential for induction of CYLD, the negative regulator of NF-kappaB: evidence for a novel inducible autoregulatory feedback pathway
    Hirofumi Jono
    Gonda Department of Cell and Molecular Biology, House Ear Institute, and Department of Otolaryngology, University of Southern California, Los Angeles, CA 90057, USA
    J Biol Chem 279:36171-4. 2004
    ..Recent studies have identified the tumor suppressor CYLD, loss of which causes a benign human syndrome called cylindromatosis, as a key negative regulator for NF-kappaB ..
  20. ncbi The bacterium, nontypeable Haemophilus influenzae, enhances host antiviral response by inducing Toll-like receptor 7 expression: evidence for negative regulation of host anti-viral response by CYLD
    Akihiro Sakai
    Department of Microbiology and Immunology, University of Rochester Medical Center, NY 14642, USA
    FEBS J 274:3655-68. 2007
    ..Interestingly, CYLD, a novel deubiquitinase, acts as a negative regulator of TLR7 induction by NTHi...
  21. pmc Tumor suppressor CYLD acts as a negative regulator for non-typeable Haemophilus influenza-induced inflammation in the middle ear and lung of mice
    Jae Hyang Lim
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America
    PLoS ONE 2:e1032. 2007
    ..The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been ..
  22. pmc Tumor suppressor cylindromatosis acts as a negative regulator for Streptococcus pneumoniae-induced NFAT signaling
    Tomoaki Koga
    Department of Microbiology and Immunology and Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 283:12546-54. 2008
    ..Interestingly, we found for the first time that tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for S...
  23. ncbi Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD
    Ato Wright
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Dev Cell 13:705-16. 2007
    ..Here we show that genetic deficiency of Cyld, a recently identified deubiquitinating enzyme, attenuates the early wave of germ cell apoptosis and causes ..
  24. pmc Inactivation of the CYLD deubiquitinase by HPV E6 mediates hypoxia-induced NF-kappaB activation
    Jiabin An
    Department of Medicine, VA Greater Los Angeles Healthcare System West Los Angeles, Los Angeles, CA 90095, USA
    Cancer Cell 14:394-407. 2008
    ..The molecular target of E6 in the NF-kappaB pathway is the CYLD lysine 63 (K63) deubiquitinase, a negative regulator of the NF-kappaB pathway...
  25. pmc Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses
    William W Reiley
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    J Exp Med 204:1475-85. 2007
    The deubiquitinating enzyme CYLD has recently been implicated in the regulation of signal transduction, but its physiological function and mechanism of action are still elusive...
  26. doi The deubiquitinating enzyme CYLD regulates the differentiation and maturation of thymic medullary epithelial cells
    Sonja Reissig
    Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany
    Immunol Cell Biol 93:558-66. 2015
    ..Previous studies identified the deubiquitinating enzyme CYLD as a critical regulator of T-cell development by activating proximal T-cell receptor signaling during ..
  27. pmc CYLD negatively regulates nontypeable Haemophilus influenzae-induced IL-8 expression via phosphatase MKP-1-dependent inhibition of ERK
    Wenzhuo Y Wang
    Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, United States of America Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America
    PLoS ONE 9:e112516. 2014
    ..We also have shown that the deubiquitinase cylindromatosis (CYLD) suppresses NTHi-induced inflammation...
  28. pmc CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN
    Diana Legarda
    Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
    Cell Rep 15:2449-61. 2016
    ..We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages...
  29. doi Myeloid-specific disruption of recombination signal binding protein Jκ ameliorates hepatic fibrosis by attenuating inflammation through cylindromatosis in mice
    Fei He
    Department of Hepatic Surgery, Xijing Hospital, Fourth Military Medical University, Xi an, China
    Hepatology 61:303-14. 2015
    ..This could be attributed to the up-regulation of cylindromatosis (CYLD), a negative regulator of NF-κB, in Notch signal-compromised macrophages, because the knockdown of CYLD in RBP-J-..
  30. doi The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
    Thibaut Eguether
    1 Institut Curie INSERM U759, Campus Universitaire, Bât 112, 91405 Orsay Cedex, France 2 Université Pierre et Marie Curie, 75005 Paris, France 3
    Nat Commun 5:4585. 2014
    b>CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63- or linear-linked ubiquitin chains...
  31. doi Cylindromatosis gene CYLD regulates hepatocyte growth factor expression in hepatic stellate cells through interaction with histone deacetylase 7
    Rajeswara R Pannem
    Department of Laboratory Medicine, Medicon Village, Lund University, Lund, Sweden
    Hepatology 60:1066-81. 2014
    ..In the present study, we identify a mechanism in which the tumor-suppressor gene, cylindromatosis (CYLD), confers protection from hepatocellular injury and fibrosis...
  32. pmc Toll-like receptor-mediated down-regulation of the deubiquitinase cylindromatosis (CYLD) protects macrophages from necroptosis in wild-derived mice
    Stephen A Schworer
    From the Graduate Program in Immunology, Medical Scientist Training Program
    J Biol Chem 289:14422-33. 2014
    ..Using a forward genetic approach in a backcross panel of mice, we identified cylindromatosis (CYLD), a deubiquitinase known to act directly on RIP1 and promote necroptosis in TNF receptor signaling, as the gene ..
  33. doi Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis
    Kim Newton
    Department of Physiological Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 343:1357-60. 2014
    ..Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis. ..
  34. pmc Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling
    Akhee S Jahan
    HKU Pasteur Research Pole and Center for Influenza Research, School of Public Health, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
    Proc Natl Acad Sci U S A 113:E705-14. 2016
    ..Our approach benefits from the use of activity-based probes in primary cells without any previous genome modification, and underscores the importance of ubiquitin-mediated regulation to refine signaling cascades. ..
  35. pmc CYLD regulates spindle orientation by stabilizing astral microtubules and promoting dishevelled-NuMA-dynein/dynactin complex formation
    Yunfan Yang
    State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China
    Proc Natl Acad Sci U S A 111:2158-63. 2014
    ..Herein, we identify a critical role for cylindromatosis (CYLD), a deubiquitinase and regulator of microtubule dynamics, in the control of spindle orientation...
  36. pmc Receptor-Interacting Protein Kinase-2 Inhibition by CYLD Impairs Antibacterial Immune Responses in Macrophages
    Katharina Wex
    Institute of Medical Microbiology and Hospital Hygiene, Otto von Guericke University Magdeburg, Magdeburg, Germany
    Front Immunol 6:650. 2015
    ..Here, we newly identify the deubiquitinating enzyme CYLD as a new inhibitor of RIPK2...
  37. pmc CYLD deubiquitinates RIP1 in the TNFα-induced necrosome to facilitate kinase activation and programmed necrosis
    David M Moquin
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 8:e76841. 2013
    ..Cylindromatosis (CYLD) is believed to promote programmed necrosis by facilitating RIP1 deubiquitination at this membrane receptor complex.
  38. pmc Hematopoietic stem cell quiescence and function are controlled by the CYLD-TRAF2-p38MAPK pathway
    Melania Tesio
    Division of Stem Cells and Cancer, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany Heidelberg Institute for Stem Cell Technology and Experimental Medicine HI STEM gGmbH, 69120 Heidelberg, Germany
    J Exp Med 212:525-38. 2015
    ..Here we show that cylindromatosis (CYLD), a tumor suppressor gene and negative regulator of NF-κB signaling with deubiquitinase activity, is highly ..
  39. doi Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report
    Demetrios N Karatzas
    School of Biology, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece
    Cell Oncol (Dordr) 39:287-93. 2016
    b>CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer...
  40. doi Deubiquitinating enzyme CYLD mediates pressure overload-induced cardiac maladaptive remodeling and dysfunction via downregulating Nrf2
    Hui Wang
    Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, SC 29208, USA
    J Mol Cell Cardiol 84:143-53. 2015
    ..Here, we uncovered a crucial role of cyclindromatosis (CYLD), a DUB, in mediating cardiac maladaptive remodeling and dysfunction...
  41. pmc CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis
    Yongge Zhao
    From the Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892
    J Biol Chem 290:22076-84. 2015
    NF-κB essential modulator (NEMO) and cylindromatosis protein (CYLD) are intracellular proteins that regulate the NF-κB signaling pathway...
  42. doi Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins
    Marie W Wooten
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 283:6783-9. 2008
    ..activity of the TRAF6-interacting the Lys63-deubiquitinating enzyme (DUB), cylindromatosis tumor suppressor (CYLD)...
  43. doi Inactivation of the deubiquitinase CYLD in hepatocytes causes apoptosis, inflammation, fibrosis, and cancer
    Kostas Nikolaou
    Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece
    Cancer Cell 21:738-50. 2012
    The tumor suppressor cylindromatosis (CYLD) inhibits the NFκB and mitogen-activated protein kinase (MAPK) activation pathways by deubiquitinating upstream regulatory factors...
  44. pmc CYLD inhibits tumorigenesis and metastasis by blocking JNK/AP1 signaling at multiple levels
    Paula Miliani de Marval
    Department of Dermatology, Duke University, Durham, North Carolina, USA
    Cancer Prev Res (Phila) 4:851-9. 2011
    b>CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear...
  45. pmc A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in vascular smooth muscle cells
    Shuai Liu
    Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012, China
    Biochem Biophys Res Commun 420:78-83. 2012
    b>CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor ..
  46. pmc The deubiquitinase CYLD targets Smad7 protein to regulate transforming growth factor β (TGF-β) signaling and the development of regulatory T cells
    Yongge Zhao
    Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 286:40520-30. 2011
    b>CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-κB and JNK signaling. Here, we show that CYLD knock-out mice have markedly increased numbers of regulatory T cells (Tregs) in peripheral lymphoid organs but not in the thymus...
  47. pmc Regulation of antiviral innate immunity by deubiquitinase CYLD
    Minying Zhang
    Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cell Mol Immunol 8:502-4. 2011
    ..Here we report that CYLD, a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains, is required for antiviral host ..
  48. pmc Negative regulation of TLR inflammatory signaling by the SUMO-deconjugating enzyme SENP6
    Xing Liu
    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    PLoS Pathog 9:e1003480. 2013
    ..onto the Lysine residue 277 of NF-κB essential modifier (NEMO/IKKγ), and this impairs the deubiquitinase CYLD to bind NEMO, thus strengthening the inhibitor of κB kinase (IKK) activation...
  49. pmc CYLD enhances severe listeriosis by impairing IL-6/STAT3-dependent fibrin production
    Gopala Nishanth
    Institute of Medical Microbiology, Otto von Guericke University Magdeburg, Magdeburg, Germany
    PLoS Pathog 9:e1003455. 2013
    ..Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-κB-dependent immune responses, regulated these protective host responses ..
  50. pmc Ubiquitin E3 ligase Itch negatively regulates osteoclast formation by promoting deubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6
    Hengwei Zhang
    Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 288:22359-68. 2013
    ..Thus, Itch is a new RANKL target gene that is induced during osteoclastogenesis. Itch interacts with the deubiquitinating enzyme and is required for deubiquitination of TRAF6, thus limiting RANKL-induced osteoclast formation. ..
  51. doi Functional inactivation of CYLD promotes the metastatic potential of tumor epidermal cells
    Josefa P Alameda
    Department of Molecular Oncology, CIEMAT, Madrid, Spain
    J Invest Dermatol 133:1870-8. 2013
    b>CYLD is a tumor-suppressor gene mutated in the skin appendage tumors cylindromas, trichoepitheliomas, and spiradenomas...
  52. pmc PKCθ/β and CYLD are antagonistic partners in the NFκB and NFAT transactivation pathways in primary mouse CD3+ T lymphocytes
    Nikolaus Thuille
    Department of Pharmacology and Genetics, Medical University of Innsbruck, Innsbruck, Austria
    PLoS ONE 8:e53709. 2013
    ..Mechanistically, we define a PKCθ-CYLD protein complex and an interaction between the positive PKCθ/β and the negative CYLD signaling pathways that both ..
  53. doi The tumor suppressor CYLD controls the function of murine regulatory T cells
    Sonja Reissig
    Institute for Molecular Medicine, Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
    J Immunol 189:4770-6. 2012
    b>CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas...
  54. doi A20 and CYLD do not share significant overlapping functions during B cell development and activation
    Yuanyuan Chu
    Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    J Immunol 189:4437-43. 2012
    The ubiquitin-editing enzyme A20 (TNFAIP3) and the deubiquitinase CYLD are central negative regulators of NF-κB signaling...
  55. doi Naturally occurring short splice variant of CYLD positively regulates dendritic cell function
    Cathy Cecilia Srokowski
    Institute for Immunology, Johannes Gutenberg University, Mainz, Germany
    Blood 113:5891-5. 2009
    Deubiquitination of NF-kappaB members by CYLD is crucial in controlling the magnitude and nature of cell activation...
  56. doi Proteasome inhibitors impair RANKL-induced NF-kappaB activity in osteoclast-like cells via disruption of p62, TRAF6, CYLD, and IkappaBalpha signaling cascades
    Estabelle Ang
    Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia
    J Cell Physiol 220:450-9. 2009
    ..pathway using selective inhibitors (MG-132, MG-115, and epoxomicin) resulted in the accumulation of p62 and CYLD, and altered the subcellular targeting and distribution of p62 and TRAF6 in osteoclast-like cells...
  57. pmc Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice
    Wei Jin
    Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    J Clin Invest 118:1858-66. 2008
    ..We therefore investigated the role of the recently identified deubiquitinating enzyme CYLD in osteoclastogenesis and found that mice with a genetic deficiency of CYLD had aberrant osteoclast ..
  58. pmc Regulation of natural killer T-cell development by deubiquitinase CYLD
    Andrew J Lee
    Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
    EMBO J 29:1600-12. 2010
    ..We show here that CYLD, a tumour suppressor with deubiquitinase function, has a pivotal and cell-intrinsic function in NKT cell ..
  59. pmc Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A
    JiHoon Chang
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 107:8340-5. 2010
    ..Unlike PP2A, MAP kinase phosphatase-1 or CYLD did not show an effect on IL-23 production supporting the specificity of PP2A...
  60. pmc Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD
    Nadine Hövelmeyer
    I Medical Department, Johannes Gutenberg University Mainz, Verfügungsgebäude, 55131 Mainz, Germany
    J Exp Med 204:2615-27. 2007
    ..We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLD(ex7/8) mice), which is a deubiquitinating enzyme that is integral to NF-kappaB signaling...
  61. pmc The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia
    Lluis Espinosa
    Cancer Research Program, Institut Municipal d Investigacions Mediques, IMIM, Hospital del Mar, 08003 Barcelona, Spain
    Cancer Cell 18:268-81. 2010
    ..Hes1 exerts its effects by repressing the deubiquitinase CYLD, a negative IKK complex regulator. CYLD expression was found to be significantly suppressed in primary T-ALL...
  62. doi Mutated cylindromatosis gene affects the functional state of dendritic cells
    Matthias Bros
    Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
    Eur J Immunol 40:2848-57. 2010
    Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling...
  63. pmc Truncation of the deubiquitinating domain of CYLD in myelomonocytic cells attenuates inflammatory responses
    Ageliki Tsagaratou
    School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
    PLoS ONE 6:e16397. 2011
    The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses...
  64. pmc Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia
    Teresa D'Altri
    Parc Recerca Biomèdica de Barcelona Barcelona, Spain
    Cell Cycle 10:1031-6. 2011
    ..We have recently shown that the Notch-Hes1-CYLD-NFkB axis is crucial in the maintenance of T-ALL, but detailed evaluation of the contribution of each one of these ..
  65. pmc Serum response factor controls CYLD expression via MAPK signaling pathway
    Gang Liang
    Department of Laboratory Medicine, Lund University, UMAS, Malmo, Sweden
    PLoS ONE 6:e19613. 2011
    Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates...
  66. doi Differential requirement of IKK2 for CYLD-dependent representation of thymic and peripheral T-cell populations
    Ageliki Tsagaratou
    School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
    Eur J Immunol 41:3054-62. 2011
    The cylindromatosis tumor suppressor gene (Cyld) encodes an enzyme (CYLD) with deubiquitinating activity that has been implicated in the regulation of thymocyte selection in an NF-κB-essential-modulator (NEMO)-dependent manner...
  67. pmc Mutant p62P392L stimulation of osteoclast differentiation in Paget's disease of bone
    Kumaran Sundaram
    Charles P Darby Children s Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA
    Endocrinology 152:4180-9. 2011
    ..Deubiquitinating enzyme cylindromatosis (CYLD) has been shown to negatively regulate RANK ligand-RANK signaling essential for OCL differentiation...