Biological Activity
Synovial apoptosis inhibitor 1/ synoviolin (SYVN1) plays a key role in various processes, such as embryogenesis or negative regulation of tumor suppressor gene p53. The expression of SYVN1 is induced by IRE1 and ATF6, during ER stress, where it protects against ER-stress induced cell apoptosis. It is a part of endoplasmic reticulum associated degradation (ERAD) and degrades 3-hydroxy-3-methylglutaryl-coenzyme A, along with TCR-α and CD3-δ, which are ERAD substrates. It also sequesters p53, in the cytoplasm, and ubiquitinates it. Thus, it represses the various activities of p53, such as cell cycle regulation and apoptosis. SYVN1 is responsible for maintaining joint homeostasis and hence, is involved in the pathogenesis of arthropathy. In rheumatoid arthritis, it is overexpressed in synovial cells, leading to a μhyper-ERADμ state. It interacts with, and degrades tau and phosphorylated tau (p-tau). Therefore, it prevents tau-induced cytotoxicity and helps neuronal survival.
