title: UV Light Potentiates STING (Stimulator of Interferon Genes)-dependent Innate Immune Signaling through Deregulation of ULK1 (Unc51-like Kinase 1).
abstract: The mechanism by which ultraviolet (UV) wavelengths of sunlight trigger or exacerbate the symptoms of the autoimmune disorder lupus erythematosus is not known but may involve a role for the innate immune system. Here we show that UV radiation potentiates STING (stimulator of interferon genes)-dependent activation of the immune signaling transcription factor interferon regulatory factor 3 (IRF3) in response to cytosolic DNA and cyclic dinucleotides in keratinocytes and other human cells. Furthermore, we find that modulation of this innate immune response also occurs with UV-mimetic chemical carcinogens and in a manner that is independent of DNA repair and several DNA damage and cell stress response signaling pathways. Rather, we find that the stimulation of STING-dependent IRF3 activation by UV is due to apoptotic signaling-dependent disruption of ULK1 (Unc51-like kinase 1), a pro-autophagic protein that negatively regulates STING. Thus, deregulation of ULK1 signaling by UV-induced DNA damage may contribute to the negative effects of sunlight UV exposure in patients with autoimmune disorders.
authors: From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 michael_kemp@med.unc.edu.
authors: Michael G
authors: MG
authors: Kemp
authors: From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
authors: Laura A
authors: LA
authors: Lindsey-Boltz
authors: From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 aziz_sancar@med.unc.edu.
authors: Aziz
authors: A
authors: Sancar
mesh_terms: D017209:Apoptosis; D015551:Autoimmunity; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014466:Ultraviolet Rays; D000099197:STING Protein
chemical_list: D000071189:Autophagy-Related Protein-1 Homolog; D050838:Interferon Regulatory Factor-3; D007372:Interferons; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; C494232:IRF3 protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C484754:ULK1 protein, human
keywords: Apoptosis; Autoimmunity; Autophagy; Cell Signaling; DNA Damage; DNA Damage Response; DNA Repair; Innate Immunity; Interferon; Nucleotide Excision Repair