| First Author | Ma C | Year | 2017 |
| Journal | EMBO Rep | Volume | 18 |
| Issue | 4 | Pages | 586-602 |
| PubMed ID | 28219902 | Mgi Jnum | J:241297 |
| Mgi Id | MGI:5901774 | Doi | 10.15252/embr.201642140 |
| Citation | Ma C, et al. (2017) NDR1 protein kinase promotes IL-17- and TNF-alpha-mediated inflammation by competitively binding TRAF3. EMBO Rep 18(4):586-602 |
| abstractText | Interleukin 17 (IL-17) is an important inducer of tissue inflammation and is involved in numerous autoimmune diseases. However, how its signal transduction is regulated is not well understood. Here, we report that nuclear Dbf2-related kinase 1 (NDR1) functions as a positive regulator of IL-17 signal transduction and IL-17-induced inflammation. NDR1 deficiency or knockdown inhibits the IL-17-induced phosphorylation of p38, ERK1/2, and p65 and the expression of chemokines and cytokines, whereas the overexpression of NDR1 promotes IL-17-induced signaling independent of its kinase activity. Mechanistically, NDR1 interacts with TRAF3 and prevents its binding to IL-17R, which promotes the formation of an IL-17R-Act1-TRAF6 complex and downstream signaling. Consistent with this, IL-17-induced inflammation is significantly reduced in NDR1-deficient mice, and NDR1 deficiency significantly protects mice from MOG-induced experimental autoimmune encephalomyelitis (EAE) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis likely by its inhibition of IL-17-mediated signaling pathway. NDR1 expression is increased in the colons of ulcerative colitis (UC) patients. Taken together, these findings suggest that NDR1 is involved in the development of autoimmune diseases. |
