Ubiquitination of overexpressed protein and enclosure by inducible ER membrane

过度表达蛋白的泛素化和诱导 ER 膜的封装

• 批准号: 17590244
• 负责人: ODA Toshiaki
• 金额: $ 2.24万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590244/
• 关键词: protein overexpression; crystalloid endoplasmic reticulum; organelle targeting signal; inducible ER; cell response; タンパク質過剰発現; タンパク質過剰産生ストレス; タンパク質の質と量の制御; ユビキチン化

It has been reported that overexpression in the culture cells of endoplasmic reticulum (ER) membrane proteins, such as microsomal aldehyde dehydrogenase (ALDH), causes the induction of a specific ER membrane structure (crystalloid ER, cER). We recently found for the first time that overexpression of an ER-unrelated, mitochondrial precursor for serine : pyruvate aminotransferase (SPT45K) induced the generation of cER, and overexpressed pOTC and pAd, other mitochondrial precursor proteins, also induced the ER aggregates. We also found that the chimeric fluorescent protein having the C terminal ER targeting sequence of ALDH at the C terminus had the remarkable ER aggregating activity by the overexpression. Because these cER (or ER aggregates) inducing activities were not observed in the cases of proteins (SPT43K, ALDHdC, EYFP) lacking organelle targeting signals, the activities is dependent on their structures. It was further indicated that the cER (ER aggregates) inducing activities was dependent on their expression levels in the cell. These data suggest that the cell has a novel system for the detection of the quality (structure) and the quantity of proteins expressed in the cytoplasm by inducing the new ER membrane structure.

据报道，内质网（ER）膜蛋白（如微粒体醛脱氢酶（ALDH））在培养细胞中的过表达会诱导特定的ER膜结构（晶体ER， cER）。我们最近首次发现，与ER无关的丝氨酸丙酮酸转氨酶线粒体前体（SPT45K）的过表达诱导了cER的产生，而其他线粒体前体蛋白pOTC和pAd的过表达也诱导了ER聚集。我们还发现，在C端具有ALDH的C端ER靶向序列的嵌合荧光蛋白通过过表达具有显著的ER聚集活性。由于在缺乏细胞器靶向信号的蛋白质（SPT43K, ALDHdC， EYFP）中没有观察到这些cER（或ER聚集物）诱导活性，因此活性依赖于它们的结构。进一步表明，ER聚集体的诱导活性依赖于其在细胞中的表达水平。这些数据表明，通过诱导新的内质网膜结构，细胞具有一种检测细胞质中表达的蛋白质质量（结构）和数量的新系统。

项目成果

Degradation of Tobl Mediated by SkP2-Dependent Ubiquitination

SkP2 依赖性泛素化介导的 Tobl 降解

• 发表时间: 2006
• 期刊: Cancer Res. 66
• 作者: Hiramatsu;Y.;Kitagawa;K.;Suzuki;T.;Uchida;C.;Hattori;T.;Kikuchi;H.;Oda T.;Hatakeyama;S.;Nakayama;KI.;Yamamoto;T.;Konno;H.;Kitagawa M.
• 通讯作者: Kitagawa M.

Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis

• DOI: 10.1158/0008-5472.can-06-2629
• 发表时间: 2006-12-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Gao, Yun;Kitagawa, Kyoko;Kitagawa, Masatoshi
• 通讯作者: Kitagawa, Masatoshi

Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury

• DOI: 10.1038/sj.ki.5000261
• 发表时间: 2006-05-01
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Fukasawa, H.;Yamamoto, T.;Hishida, A.
• 通讯作者: Hishida, A.

Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: Sequential analyses

• DOI: 10.1111/j.1349-7006.2006.00154.x
• 发表时间: 2006-02-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Kikuchi, H;Yamashita, K;Konno, H
• 通讯作者: Konno, H

Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia

与铜蓝蛋白血症相关的铜蓝蛋白基因突变的生化特征

• 发表时间: 2006
• 期刊: Neuromol. Med. 8
• 作者: Kono;S.;Suzuki;H.;Oda;T.;Miyajima;H.;Takahashi;Y.;Shirakawa;K.;Ishikawa;K.;Kitagawa;M.
• 通讯作者: M.