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型应激蛋白HSP47的基因，该基因位于内质网（ER）中，该基因在胶原生物合成，加工和分泌的途径中充当胶原特异性分子伴侣。除了与胶原蛋白的结合特异性外，HSP47的表达始终与小鼠胚胎正常发育以及包括肝纤维化的病理生理条件以及包括ERQC（ER质量控制）（包括ER相关的降解）在内的病理生理状况密切相关。我们已经克隆了一个小鼠基因EDEM和EDEM家族蛋白，这些蛋白与糖蛋白的脱落有关。此外，我们还确定并克隆的ERDJ5是ER中含有ER的含有伴有伴侣蛋白的依克蛋白蛋白的ERDJ5，我们表明的是ER中的ERAD，作为ER中的一种新还原酶。我们还研究了胞质蛋白伴侣蛋白CCT，并显示CCT可预防含有多糖蛋白的聚集。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

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.

The endoplasmic reticulum stress response is stimulated through the continuous activation of transcrption factors ATF6 and XBP1 in Ins2^<+/Akita> pancreatic b ceils.

Ins2^<Akita>胰腺b细胞中转录因子ATF6和XBP1的持续激活刺激内质网应激反应。

• 发表时间: 2004
• 期刊: Genes Cells 9
• 作者: A.Ikeda;KItoh;T.Suzuki;M.Aida;Y.Fujii;T.Mitsugashira;M.Hara;M.Ozawa;J.NOZAKI et al.
• 通讯作者: J.NOZAKI et al.

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

EDEM3, a soluble EDEM homolog, enhances glycoprotein ERAD and mannose trimming.

EDEM3 是一种可溶性 EDEM 同系物，可增强糖蛋白 ERAD 和甘露糖修剪。

• 发表时间: 2006
• 期刊: J Biol Chem 281・14
• 作者: Tomoichi Yokozeki;Kazuyoshi Hirao
• 通讯作者: Kazuyoshi Hirao

Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.

• DOI: 10.1083/jcb.200507057
• 发表时间: 2006-01-30
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Oda, Yukako;Okada, Tetsuya;Yoshida, Hiderou;Kaufman, Randal J;Nagata, Kazuhiro;Mori, Kazutoshi
• 通讯作者: Mori, Kazutoshi