Hippo kinase NDR2 inhibits IL-17 signaling by promoting Smurf1-mediated MEKK2 ubiquitination and degradation.

Autor: Ma X; Cancer Institute, Institute of Translational Medicine, Second Military Medical University, Shanghai, 200433, China; Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China. Electronic address: mxw5688@aliyun.com., Wang D; Department of Gynaecology and Obstetrics, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: wangdanown@163.com., Li N; Department of Anesthesiology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: lee3072007@163.com., Gao P; Cancer Institute, Institute of Translational Medicine, Second Military Medical University, Shanghai, 200433, China. Electronic address: 277986249@qq.com., Zhang M; Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China. Electronic address: ailiszhang@163.com., Zhang Y; Department of Anesthesiology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: zhangyansmmu@163.com.
Jazyk: angličtina
Zdroj: Molecular immunology [Mol Immunol] 2019 Jan; Vol. 105, pp. 131-136. Date of Electronic Publication: 2018 Nov 30.
DOI: 10.1016/j.molimm.2018.10.005
Abstrakt: NDR/LATS kinase family are conserved from yeast to man and their roles in inflammation remains largely unknown. In the present study, we show that knockdown of NDR2 significantly increases IL-17-induced IL-6, CXCL2 and CCL20 expression in Hela and HT-29 cells. Knockdown of NDR2 enhances IL-17-induced MAPK and NF-κB activation. NDR2 interacts with E3 ubiquitin protein ligase Smurf1, promotes Smurf1-mediated K48-linked ubiquitination of MEKK2 and inhibits expression of MEKK2. Consistently, knockdown of Smurf1 increases IL-17-induced IL-6, CXCL2 and CCL20 expression. On the other hand, overexpression of MEKK2 increases IL-17-induced IL-6 expression. These results suggest that NDR2 may play important roles in IL-17-associated inflammation by promoting Smurf1-mediated MEKK2 ubiquitination and degradation.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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