Synoviolin meets metabolic disorders

Excerpt

Rheumatoid arthritis (RA) is consists of multiple processes such as chronic inflammation, overgrowth of synovial cells, joint destruction and fibrosis. To clarify the mechanism of outgrowth of synovial cells, we carried out immunoscreening using anti-rheumatoid synovial cell antibody, and cloned 'Synoviolin' [1]. Synoviolin is endoplasmic reticulum (ER)-resident E3 ubiquitin ligases, and is involved in ER-associated degradation (ERAD). Synoviolin is highly expressed in synoviocytes of patients with RA. Overexpression of synoviolin in transgenic mice leads to advanced arthropathy caused by reduced apoptosis of synoviocytes [1]. We postulate that the hyperactivation of the ERAD pathway by overexpression of synoviolin results in prevention of ER-stress-induced apoptosis leading to synovial hyperplasia [2]. In addition, Synoviolin ubiquitinates and sequesters the tumor suppressor p53 in the cytoplasm, thereby negatively regulating its biological functions [3]. Therefore Synoviolin regulates, not only apoptosis in response to ER stress, but also a p53-dependent apoptotic pathway. These studies indicate that Synoviolin is involved in overgrowth of synovial cells through its anti-apoptotic effects. Further analysis showed that Synoviolin is also involved in fibrosis among the multiple processes [4]. Therefore, it was suggested that Synoviolin is thought to be a candidate for pathogenic factor for arthropathy through its involvement of multiple processes. …