Relationship of post-translational modifications in RA synoviocytes

我们以前克隆的E3泛素连接酶，Synoviolin，作为滑膜细胞增殖的调节因子在类风湿关节炎（RA），并建议内质网（ER）相关的降解系统通过Synoviolin滑膜细胞的过度生长具有重要作用。已知蛋白质的瓜氨酸在RA中被激活，并且肽基精氨酸脱亚胺酶4（PADI 4）被鉴定为RA易感基因。关于这些翻译后修饰，我们揭示了它们与瓜氨酸相关，瓜氨酸可以减少滑膜蛋白和内质网应激引起的泛素化。本研究建立了滑膜素条件性基因敲除小鼠和滑膜素酶抑制剂，并在体内研究了滑膜素翻译后修饰的功能。

We previously cloned E3 ubiquitin ligase, Synoviolin, as a regulatory factor of synoviocytes proliferation in rheumatoid arthritis (RA) and suggested that endoplasmic reticulum (ER) associated degradation system via Synoviolin has important roles for overgrowth of synoviocytes. It is known that the citrullination of proteins is activated in RA and Peptidyl-Arginine Deiminases 4 (PADI4) is identified as the RA-susceptible gene. In regard to these post-trasnslational modifications, we revealed that they associate and citrullination could decrease the ubiquitination by synoviolin and ER stress. In this study, I established synoviolin conditional knockout mice and enzymatic inhibitors of synoviolin and explored the function of post-translational modifications in vivo.