title: 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.
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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
authors.forename: Shengqing
authors.initials: S
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Tatyana
authors.initials: T
authors.lastname: Zykova
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Cho
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Weiya
authors.initials: W
authors.lastname: Ma
authors.forename: Andria
authors.initials: A
authors.lastname: Carper
authors.forename: Alyssa
authors.initials: A
authors.lastname: Langfald
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003872:Dermatitis / Q000201:enzymology* / Q000235:genetics; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability / Q000235:genetics / Q000528:radiation effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000528:radiation effects*; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation / Q000235:genetics / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000201:enzymology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse