Cell cycle regulation by protein degradation and transport

通过蛋白质降解和运输调节细胞周期

• 批准号: 13043006
• 负责人: TOH-E Akio
• 金额: $ 76.03万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13043006/
• 关键词: 26S proteasome; 19S reguratory comoplex; base; baker's yeast; lid; RPN7; RPN6; RPN5; ユビキチン・プロテアソーム系; サブユニット集合; RPN8; 局在; 出芽酵母; ユビキチン; M期後期開始; RPN9; 蛋白質分解; G2; Mアレスト; プロテアソーム; 阻害剤; M期終了; Cdc14; 核小体; MEN; Tem1; SPB; スピンドルチェックポイント

It is widely accepted that the ubiquitin-proteasome system plays a pivotal role in degradation of short-lived proteins, many of them are regulatory proteins, in an energy dependent manner. The 26S proteasome is responsible to the final step of proteolysis in this system. The 26S proteasome is a large protein complex consisting of 20S proteasome containing active sites and 19S regulatory factor called as 19S RP. The basic subunit composition has been elucidated. By exploiting this information, we started uncovering how and where these subunits assemble together. We focused on the 19S RP of Saccharomyces cerevisiae. The 19S RP consists of two sub-complexes, the lid and the base. We isolated temperature-sensitive mutants of the genes encoding subunits of the lid. Biochemical characterization revealed that hierarchy of the assembly of the lid, and the lid and the base are constructed independently of each other. We also examined localization of each sub-complex in various mutants and found that the base and the lid can separately be localized in the nucleus. The 19S RP too is localized in the nucleus and assembles with the 20S proteasome to the 26S proteasome.

人们普遍认为，泛素-蛋白酶体系统在降解短寿命蛋白质中起着关键作用，其中许多蛋白质是调节蛋白，并以能量依赖的方式降解。26S蛋白酶体负责该系统中蛋白分解的最后一步。26S蛋白酶体是由含有活性部位的20S蛋白酶体和19S调节因子组成的一个大的蛋白质复合体，称为19S RP。基本亚基组成已被阐明。通过利用这些信息，我们开始揭示这些亚单位是如何以及在哪里组装在一起的。我们对酿酒酵母的19S RP进行了研究。19S RP由两个子复合体组成，盖子和底座。我们分离了编码LID亚单位的基因的温度敏感型突变体。生化表征表明，盖子的组装层次以及盖子和底座是彼此独立构造的。我们还检查了每个亚复合体在各种突变体中的定位，发现碱基和盖子可以分别定位在细胞核中。19S RP也定位于细胞核，与20S蛋白酶体和26S蛋白酶体组装在一起。

项目成果

Yease Pho85 kinase is required for proper gene expression during the diauxic shift

Yease Pho85 激酶是双轴转变期间正确基因表达所必需的

• 发表时间: 2004
• 期刊: Yeast 21
• 作者: Nishizawa;M.;et al.
• 通讯作者: et al.

Yoshida, S., Asakawa, K., Toh-e, A.: "Mitotic exit network controls the localization of Cdc14 to the spindle pole body in Saccharomyces cerevisiae"Curr.Biol.. 12. 944-950 (2002)

Yoshida, S.、Asakawa, K.、Toh-e, A.：“有丝分裂出口网络控制 Cdc14 在酿酒酵母中纺锤体极体的定位”Curr.Biol.. 12. 944-950 (2002)

Mmrlp is a mitochondrial factor for Myo2p-dependent inheritance of mitochondria in the budding yeast

Mmrlp 是芽殖酵母中 Myo2p 依赖性线粒体遗传的线粒体因子

• 发表时间: 2004
• 期刊: EMBO J. 23
• 作者: Itoh;T.
• 通讯作者: T.

A role for Ltelp (a low Tempperatur Esssential Protein involved in Mitosis) in proprotein processing in the yeast secretory pathway.

Ltelp（一种参与有丝分裂的低温必需蛋白）在酵母分泌途径中前蛋白加工中的作用。

• 发表时间: 2007
• 期刊: J. Biol. Chem. 282
• 作者: Zhao;X.;et al.
• 通讯作者: et al.

Yoshida, S., Ichihashi, R., Toh-e, A.: "Ras recruits mitotic exit regulator Lte1 to the bud cortex in budding yeast"J.Cell Biol.. (印刷中). (2003)

Yoshida, S.、Ichihashi, R.、Toh-e, A.：“Ras 将有丝分裂退出调节因子 Lte1 招募到芽殖酵母中的芽皮层”J.Cell Biol..（出版中）。