中国科学院分子细胞科学卓越创新中心沈义栋研究组揭示了COPII囊泡的破坏通过SEC-23激活HSF-1。相关论文于2025年7月3日发表在《分子细胞生物学报》杂志上。

该团队发现，在秀丽隐杆线虫和NIH3T3细胞中，HSF-1通过与核心COPII成分SEC-23的相互作用，直接监测COPII囊泡功能障碍。抑制SEC-23或SAR-1可破坏COPII囊泡的形成，导致HSF-1从COPII复合体中释放。这种释放诱导特定的转录组变化以恢复蛋白质稳态。他们的发现揭示了HSF-1响应COPII囊泡失调的保守机制，为以HSF-1为中心的蛋白质停滞网络提供了新的见解。

据了解，HSF-1是一种高度保守的转录因子，在保护生物体免受各种细胞应激中起着核心作用。然而，HSF-1感知和响应不同类型压力的机制仍然不完全清楚。COPII包被的囊泡负责将货物从内质网运送到高尔基体，对蛋白质分泌和细胞稳态至关重要。这些囊泡的破坏会损害蛋白质分泌并引发严重的蛋白质毒性应激。

附：英文原文

Title: The disruption of COPII vesicles activates HSF-1 through SEC-23

Author: He, Zhidong, Tang, Na, Liu, Hao, Wang, Xueqing, Yin, Yue, Peng, Chao, Shen, Yidong

Issue&Volume: 2025-07-03

Abstract: HSF-1 is a highly conserved transcription factor that plays a central role in protecting organisms from diverse cellular stresses. However, the mechanisms by which HSF-1 senses and responds to different types of stress remain incompletely understood. COPII-coated vesicles, responsible for transporting cargo from the endoplasmic reticulum to the Golgi apparatus, are essential for protein secretion and cellular homeostasis. Disruption of these vesicles impairs protein secretion and triggers severe proteotoxic stress. Here, we show that HSF-1 directly monitors COPII vesicle dysfunction through interactions with the core COPII component SEC-23, in both Caenorhabditis elegans and NIH3T3 cells. Inhibition of SEC-23 or SAR-1 disrupts COPII vesicle formation, leading to the release of HSF-1 from the COPII complex. This release induces a specific transcriptomic change to restore protein homeostasis. Our findings reveal a conserved mechanism by which HSF-1 responds to COPII vesicle dysregulation, providing new insights into the HSF-1-centered proteostasis network.

DOI: 10.1093/jmcb/mjaf017

Source: https://academic.oup.com/jmcb/advance-article/doi/10.1093/jmcb/mjaf017/8185395?searchresult=1