Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 34, Pages 29601-29609Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.225813
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Funding
- National Institutes of Health [CA120388, R37 CA081064, ES016548]
- Hormel Foundation
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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 UVlight-induced inflammation. In this study, we found that TOPK negatively regulated the activity of p38 alpha by phosphorylating the p38 alpha-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.
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