Quality control mechanism for positive and negative

我们发现并克隆了一种新的应激蛋白HSP47的基因，它位于内质网(ER)中，在胶原的生物合成、加工和分泌过程中扮演着胶原特异性分子伴侣的角色。除了与胶原的结合特异性外，HSP47在小鼠胚胎的正常发育过程中以及在肝肾纤维化等病理生理条件下的表达总是与胶原的表达密切相关。我们还在研究ERQC(内质网质量控制)的细胞内机制，包括ERAD(内质网相关降解)。我们已经克隆了小鼠基因EDEM和参与糖蛋白ERAD的EDEM家族蛋白。此外，我们还鉴定并克隆了ERdj5，它是内质网中与EDEM结合的含有J结构域的伴侣样蛋白，我们发现它作为一种新的内质网还原酶参与ERAD。我们还在研究胞质伴侣蛋白CCT，结果表明CCT阻止了含有聚谷氨酰胺的蛋白的聚集。这一发现与神经退行性疾病的治疗策略的发展直接相关。

We found and cloned the gene of a novel stress protein HSP47 which resides in the endoplasmic reticulum (ER) acting as a collagen-specific molecular chaperone in the pathway of collagen biosynthesis, processing and secretion. In addition to the binding specificity to collagen, the expression of HSP47 is always closely correlated with those of collagens during the normal development of mouse embryo as well as in the pathophysiological conditions including liver and renal fibrosis.We are also working on the intracellular mechanism of ERQC (ER quality control) including ERAD (ER associated degradation). We have cloned a mouse gene EDEM, and EDEM family proteins, which are involved in the ERAD of glycoproteins. Furthermore, we also identified and cloned ERdj5 as EDEM-binding J-domain-containing chaperone-like protein in the ER, which we showed is involved in ERAD as a novel reductase in the ER.We are also studying cytosolic chaperonin CCT and showed that CCT prevents the aggregation of poly-glutamine containing proteins. This finding is directly related to the development of therapeutic strategy for neurodegenerative diseases.