Scholarlink

<p>The attachment of Post-Translational Modifications (PTMs) to proteins regulates their activities and stability. Here we utilized the nematode <i>Caenorhabditis elegans</i> to test whether UFMylation, a PTM which affects key biological functions, regulate aging and protein homeostasis (proteostasis). We find that lowering UFMylation extends lifespan and mitigates the toxicity of aggregation-prone proteins that underlie the development of neurodegenerative disorders in humans. Mass spectrometric analysis suggests that UFMylation of aging-regulating proteins, including of the nucleolar FIB-1-NOL-56 complex and the germline-resident proteins CAR-1 and CGH-1, governs proteostasis, probably across tissues. Functional analyses indicate that the proteostasis-regulating transcription factors DAF-16 and SKN-1 are crucial for the protective effects of reduced UFMylation. Counter-proteotoxic effect of reduced UFMylation are mediated by enhanced nascent protein quality control, reduced protein aggregation, and increased protein degradation by the ubiquitin–proteasome system. These insights highlight the important roles of PTMs in the regulation of proteostasis and point at research directions for the development of therapies for neurodegenerative disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Aging-associated modulation of UFMylation impairs proteostasis in C. elegans

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月29日

查看全文
  • Reut Bruck-Haimson,
  • Hana Boocholez,
  • Huadong Zhu,
  • Adam Zaretsky,
  • Irit Cohen,
  • Xiaofeng Feng,
  • Yong-Hong Yan,
  • Meng-Qiu Dong,
  • Ehud Cohen

摘要

The attachment of Post-Translational Modifications (PTMs) to proteins regulates their activities and stability. Here we utilized the nematode Caenorhabditis elegans to test whether UFMylation, a PTM which affects key biological functions, regulate aging and protein homeostasis (proteostasis). We find that lowering UFMylation extends lifespan and mitigates the toxicity of aggregation-prone proteins that underlie the development of neurodegenerative disorders in humans. Mass spectrometric analysis suggests that UFMylation of aging-regulating proteins, including of the nucleolar FIB-1-NOL-56 complex and the germline-resident proteins CAR-1 and CGH-1, governs proteostasis, probably across tissues. Functional analyses indicate that the proteostasis-regulating transcription factors DAF-16 and SKN-1 are crucial for the protective effects of reduced UFMylation. Counter-proteotoxic effect of reduced UFMylation are mediated by enhanced nascent protein quality control, reduced protein aggregation, and increased protein degradation by the ubiquitin–proteasome system. These insights highlight the important roles of PTMs in the regulation of proteostasis and point at research directions for the development of therapies for neurodegenerative disorders.