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KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation.

Karina C LockwoodTravis B LearShristi RajbhandariAlison C McKelveySarah R DunnÁine N BoudreauYuan LiuBill B Chen
Published in: The FEBS journal (2023)
Dysregulated cytokine signaling is a hallmark of inflammatory bowel diseases. Inflammatory responses of the colon are regulated by suppressor of cytokine signaling (SOCS) proteins. SOCS1 is a key member of this family, and its function is critical in maintaining an appropriate inflammatory response through the JAK/STAT signaling pathway. Dysregulation of SOCS1 protein has been identified as a causal element in colonic inflammatory diseases. Despite this, it remains unclear how SOCS1 protein is regulated. Here, we identify that SOCS1 protein is targeted for degradation by the ubiquitin proteasome system, mediated by the E3 ubiquitin ligase KIAA0317 during experimental colonic inflammation. We characterize the mechanism of protein-protein interaction and ubiquitin conjugation to SOCS1 and demonstrate that modulation of SOCS1 protein level leads to stark effects on JAK/STAT inflammatory signaling. Together, these results provide insight into the regulation of colonic inflammation through a new mechanism of ubiquitin-based control of SOCS1 protein.
Keyphrases
  • protein protein
  • small molecule
  • oxidative stress
  • inflammatory response
  • signaling pathway
  • amino acid
  • binding protein
  • transcription factor
  • lipopolysaccharide induced
  • toll like receptor
  • cell proliferation