Quality control mechanism for positive and negative

正反质量控制机制

• 批准号: 16207013
• 负责人: NAGATA Kazuhiro
• 金额: $ 32.12万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16207013/
• 关键词: Molecular Chaperone; Quality control; ER associated degradation; EDEM

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.

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。

项目成果

Specific recognition of the collagen triple helix by chaperone HSP47 - Minimal structural requirement and spatial molecular orientation

• DOI: 10.1074/jbc.m509707200
• 发表时间: 2006-02-10
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Koide, T;Asada, S;Kitagawa, K
• 通讯作者: Kitagawa, K

Type I collagen in Hsp47-null cells is aggregated in ER and deficient in N-propeptide processing and fibrillogenesis

Hsp47 缺失细胞中的 I 型胶原蛋白聚集在 ER 中，并且缺乏 N 前肽加工和原纤维形成

• 发表时间: 2006
• 期刊: Mol. Biol. Cell. 17
• 作者: Luo;B. H.;Carman;C. V.;Takagi;J.;Springer;T. A;K.Nagasawa;T.Koide;Y.Oda;K.Hirao;N.Hosokawa;Y.Ishida
• 通讯作者: Y.Ishida

Accumulation of type IV collagen in dilated endoplasmic reticulum leads to apoptosis HSP47-knockout mouse embryos through the induction of CHOP

IV型胶原在扩张内质网中的积累通过诱导CHOP导致HSP47敲除小鼠胚胎凋亡

• 发表时间: 2004
• 期刊: J. Cell. Sci. 117
• 作者: Akio Kato;Shigeru Utsumi;Toshihiko Utsumi;Yasushi Kawata;Yuriko Yamagata;Akihiko Yamagishi;Masaaki Yoshikawa;Y. Matsuoka;河田康志(加藤昭夫編集);T. Marutani
• 通讯作者: T. Marutani

Characterization of multiple members of the HSP7O family in platyfish culture cells : molecular evolution of stress protein HSP7O in vertebrates.

扁鱼培养细胞中 HSP7O 家族多个成员的表征：脊椎动物应激蛋白 HSP7O 的分子进化。

• 发表时间: 2004
• 期刊: Gene 336
• 作者: T.Suzuki;A.Ikeda;K.Itoh;M.Aida;Y.Fujii;M.Hara;T.Mitsugashira;M.Ozawa;Matushita S.;M.YAMASHITA et al.
• 通讯作者: M.YAMASHITA et al.

Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands.

• 发表时间: 2006
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: S. Kubota;H. Kubota;K. Nagata