Relationship of post-translational modifications in RA synoviocytes

我们先前克隆了E3泛素连接酶Synoviolin作为类风湿关节炎（RA）滑膜细胞增殖的调节因子，并提示内质网（ER）相关降解系统通过syno小提琴对滑膜细胞的过度生长起重要作用。已知在RA中蛋白的瓜氨酸化被激活，肽基精氨酸脱亚胺酶4 （PADI4）被确定为RA易感基因。对于这些翻译后修饰，我们发现它们的关联和瓜氨酸化可以降低滑膜和内质网应激下的泛素化。在本研究中，我建立了滑膜小提琴条件敲除小鼠和滑膜小提琴的酶抑制剂，并在体内探索了翻译后修饰的功能。

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.