Hippo 激酶 NDR2 通过促进 Smurf1 介导的 MEKK2 泛素化和降解来抑制 IL-17 信号通路。
Hippo kinase NDR2 inhibits IL-17 signaling by promoting Smurf1-mediated MEKK2 ubiquitination and degradation.
机构信息
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.
Department of Gynaecology and Obstetrics, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
出版信息
Mol Immunol. 2019 Jan;105:131-136. doi: 10.1016/j.molimm.2018.10.005. Epub 2018 Nov 30.
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.
NDR/LATS 激酶家族在从酵母到人中都得到了保守，但其在炎症中的作用在很大程度上仍不清楚。在本研究中，我们表明 NDR2 的敲低显著增加了 Hela 和 HT-29 细胞中 IL-17 诱导的 IL-6、CXCL2 和 CCL20 的表达。NDR2 的敲低增强了 IL-17 诱导的 MAPK 和 NF-κB 激活。NDR2 与 E3 泛素蛋白连接酶 Smurf1 相互作用，促进 Smurf1 介导的 MEKK2 的 K48 连接泛素化，并抑制 MEKK2 的表达。一致地，Smurf1 的敲低增加了 IL-17 诱导的 IL-6、CXCL2 和 CCL20 的表达。另一方面，MEKK2 的过表达增加了 IL-17 诱导的 IL-6 表达。这些结果表明，NDR2 可能通过促进 Smurf1 介导的 MEKK2 泛素化和降解，在 IL-17 相关炎症中发挥重要作用。
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