title: Activation of oxidative stress-regulated Bcl-3 suppresses CTCF in corneal epithelial cells.
abstract: Epigenetic factor CTCF (CCCTC binding factor) plays important roles in genetic controls of the cell fate. Previous studies found in corneal epithelial cells that CTCF is regulated by epidermal growth factor (EGF) through activation of NF-κB p65/p50. It also found that CTCF is suppressed in ultraviolet (UV) stress-induced corneal epithelial cells. However, it is still unknown how UV stress down-regulates CTCF affecting the cell fate. In the present study, we report that regulation of CTCF by extracellular stress signals is dependent upon activations of an oxidative stress-regulated protein Bcl-3. We found that activated Bcl-3 was able to bind to the κB sites identified in the CTCF promoter region. Bcl-3 was activated by UV irradiation to interact with NF-κB p50 by forming a Bcl-3/p50 heterodimer complex. The Bcl-3/p50 complex suppressed CTCF promoter activity to down-regulate CTCF transcription. Unlike the effect of EGF, UV stress-induced Bcl-3 activation suppressed CTCF activity without involving the IκBα and p65 pathway. Thus, results of the study reveal a novel mechanism for regulatory control of CTCF in UV stress-induced human corneal epithelial cells, which requires activation and formation of Bcl-3/p50 complex through a noncanonical NF-κB pathway.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Torrance, California, United States of America.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.forename: Luo
authors.initials: L
authors.lastname: Lu
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D000076246:CCCTC-Binding Factor; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization / Q000187:drug effects / Q000528:radiation effects; D020836:Protein Structure, Quaternary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D051550:I-kappa B Kinase