title: UV Irradiation Triggers Cylindromatosis Translocation, Modification, and Degradation in a Proteasome-Independent Manner.
abstract: The tumor suppressor, cylindromatosis (CYLD), is a negative regulator of NF-κB signaling by removing lysine 63-linked ubiquitin chains from multiple NF-κB signaling components, including TRAF2, TRAF6, and NEMO. How CYLD itself is regulated, however, remains yet to be characterized. In this study, we present the first evidence that UV irradiation is able to induce CYLD translocation from the cytoplasm to microtubules and that the cytoskeleton-associated CYLD is subject to posttranslational modification and degradation in a proteasome-independent manner. By immunostaining, we found that CYLD displayed microtubule-like filament localization under ultraviolet (UV) irradiation. Further studies revealed that the cytoskeleton-associated CYLD underwent posttranslational modification, which in turn contributed to CYLD degradation in an unknown manner, distinct from proteasome-mediated degradation under normal conditions. Collectively, our data suggest that UV-induced CYLD degradation might serve as an underlying mechanism for UV-induced NF-κB pathway activation.
authors.affiliation: 1 Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Ministry of Education and Tianjin, Tianjin University of Science and Technology , Tianjin, China .
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Hao
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Xincheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Jinmin
authors.initials: J
authors.lastname: Gao
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.affiliation: 1 Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Ministry of Education and Tianjin, Tianjin University of Science and Technology , Tianjin, China .|3 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China .
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D003599:Cytoskeleton / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D006367:HeLa Cells / Q000528:radiation effects; D006801:Humans; D061986:MCF-7 Cells / Q000528:radiation effects; D008870:Microtubules / Q000378:metabolism / Q000528:radiation effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D046988:Proteasome Endopeptidase Complex