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T-LAK cell-originated protein kinase (TOPK) phosphorylation of MKP1 protein prevents solar ultraviolet light-induced inflammation through inhibition of the p38 protein signaling pathway
Authors:Li Shengqing  Zhu Feng  Zykova Tatyana  Kim Myoung Ok  Cho Yong Yeon  Bode Ann M  Peng Cong  Ma Weiya  Carper Andria  Langfald Alyssa  Dong Zigang
Institution:The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Abstract:Solar UV radiation is a major environmental factor that causes DNA damage, inflammation, and even skin cancer. T-LAK cell-originated protein kinase (TOPK) is expressed widely in both normal and cancer cells and functions to inhibit apoptosis and promote carcinogenesis. However, its function in inflammation is not known. The p38 MAPK signaling pathway plays an important role in solar UV light-induced inflammation. In this study, we found that TOPK negatively regulated the activity of p38α by phosphorylating the p38α-specific phosphatase MKP1 and enhancing the stability of MKP1. Notably, the absence of TOPK in mice resulted in a striking increase in skin inflammation. Therefore, we conclude that TOPK has a protective function in solar UV light-induced inflammation.
Keywords:Cancer Tumor Promoter  Cyclooxygenase (COX) Pathway  MAP Kinases (MAPKs)  p38  Tumor Necrosis Factor (TNF)  Solar Ultraviolet (UV) Radiation  TOPK
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