Multiubiquitylation Pathways Involved in Muscle Assembly

参与肌肉组装的多泛素化途径

• 批准号: 18857872
• 负责人: Professor Dr. Thorsten Hoppe
• 金额: --
• 依托单位: Institut für Genetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/18857872?language=en
• 关键词: Multiubiquitylation; Pathways; Involved; Muscle; Assembly

The ubiquitin/proteasome system is pivotal for the elimination of misfolded proteins, and defects in this pathway can result in the pathogenesis of diseases such as skeletal muscle atrophy. Besides the already known E1, E2 and E3 enzymes, which are catalysts for substrate ubiquitylation, additional multiubiquitin chain elongation factors have been identified and named E4. Our recent work revealed a novel functional interaction between the Caenorhabditis elegans orthologs of the E4 enzymes CHIP and UFD2, CHN-1 and UFD-2, respectively. The E3/E4- multiubiquitylation complex formed by CHN-1 and UFD-2 regulates the stability of the myosin specific chaperone UNC-45. The central objective of our proposed research is to define the mechanism by which UFD-2/CHN-1 complex formation ensures multiubiquitylation of UNC-45 and how this is linked to myosin assembly into striated muscles.

泛素/蛋白酶体系统对于消除错误折叠的蛋白质是关键的，并且该途径中的缺陷可导致诸如骨骼肌萎缩的疾病的发病机制。除了已知的E1、E2和E3酶（它们是底物泛素化的催化剂）之外，还鉴定了另外的多泛素链延长因子并命名为E4。我们最近的工作揭示了E4酶CHIP和UFD 2，CHN-1和UFD-2的秀丽隐杆线虫直向同源物之间的新的功能相互作用。由CHN-1和UFD-2形成的E3/E4-多泛素化复合物调节肌球蛋白特异性伴侣蛋白α-45的稳定性。我们所提出的研究的中心目标是确定UFD-2/CHN-1复合物形成的机制，以确保α-45的多泛素化，以及这是如何与肌球蛋白组装成横纹肌。

项目成果

Less is more: how protein degradation regulates muscle development.

少即是多：蛋白质降解如何调节肌肉发育

• DOI: 10.1007/2789_2008_101
• 发表时间: 2009
• 期刊: Ernst Schering Foundation symposium proceedings
• 作者: Hoppe T.

The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to human myopathy

• DOI: 10.1038/ncb1554
• 发表时间: 2007-04-01
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Janiesch, Philipp Christoph;Kim, Johnny;Hoppe, Thorsten
• 通讯作者: Hoppe, Thorsten

The Ubiquitin Proteasome System and Muscle Development

泛素蛋白酶体系统和肌肉发育

• DOI: 10.1002/9783527620227.ch2
• 发表时间: 2006
• 作者: Kim J.;Hoppe T.
• 通讯作者: Hoppe T.