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

被引:42
|
作者
Li, Shengqing [1 ]
Zhu, Feng [1 ]
Zykova, Tatyana [1 ]
Kim, Myoung Ok [1 ]
Cho, Yong Yeon [1 ,2 ]
Bode, Ann M. [1 ]
Peng, Cong [1 ]
Ma, Weiya [1 ]
Carper, Andria [1 ]
Langfald, Alyssa [1 ]
Dong, Zigang [1 ,2 ]
机构
[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA
[2] Catholic Univ Korea, Coll Pharm, Puchon, Gyeonggi Do, South Korea
基金
美国国家卫生研究院;
关键词
PHOSPHATASE-MEDIATED CROSSTALK; COLORECTAL-CANCER CELLS; RPMI7951; MELANOMA-CELLS; MAP KINASE; INDUCED APOPTOSIS; BREAST-CANCER; P38-ALPHA; SKIN; MICE; PROLIFERATION;
D O I
10.1074/jbc.M111.225813
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:29601 / 29609
页数:9
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