UV Light Potentiates STING (Stimulator of Interferon Genes)-dependent Innate Immune Signaling through Deregulation of ULK1 (Unc51-like Kinase 1)

J Biol Chem. 2015 May 8;290(19):12184-94. doi: 10.1074/jbc.M115.649301. Epub 2015 Mar 19.


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.

Keywords: Apoptosis; Autoimmunity; Autophagy; Cell Signaling; DNA Damage; DNA Damage Response; DNA Repair; Innate Immunity; Interferon; Nucleotide Excision Repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis
  • Autoimmunity
  • Autophagy
  • Autophagy-Related Protein-1 Homolog
  • Cell Line
  • DNA Damage
  • DNA Repair
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Immunity, Innate*
  • Interferon Regulatory Factor-3 / metabolism
  • Interferons / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Keratinocytes / metabolism
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Signal Transduction
  • Ultraviolet Rays*


  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • STING1 protein, human
  • Interferons
  • Autophagy-Related Protein-1 Homolog
  • Protein Serine-Threonine Kinases
  • ULK1 protein, human