Abstract
Abstract Solar ultraviolet (UV) irradiation is a major environmental factor that causes DNA damage, inflammation, and skin cancer. T-LAK cell-originated protein kinase (TOPK) is widely expressed 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. The phosphorylation level of p38 was reported to be up-regulated after transfection of the TOPK gene into COS-7 cells. We found that the phosphorylation level of p38α was increased in TOPK-/- mouse embryonic fibroblasts (MEFs) compared with TOPK+/+ MEFs after stimulation with solar UV light. Our observations unveil a novel role for TOPK. We found that TOPK negatively regulated the activity of p38α by phosphorylating the p38α-specific phosphatase MKP1 and enhancing the stability of MPK1. 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 224. doi:1538-7445.AM2012-224
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