Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Trends Biochem Sci. 2022 Mar;47(3):218-234. doi: 10.1016/j.tibs.2021.10.004. Epub 2021 Nov 19.
To thrive and to fulfill their functions, cells need to maintain proteome homeostasis even in the face of adverse environmental conditions or radical restructuring of the proteome during differentiation. At the center of the regulation of proteome homeostasis is an ancient transcriptional mechanism, the so-called heat shock response (HSR), orchestrated in all eukaryotic cells by heat shock transcription factor 1 (Hsf1). As Hsf1 is implicated in aging and several pathologies like cancer and neurodegenerative disorders, understanding the regulation of Hsf1 could open novel therapeutic opportunities. In this review, we discuss the regulation of Hsf1's transcriptional activity by multiple layers of control circuits involving Hsf1 synthesis and degradation, conformational rearrangements and post-translational modifications (PTMs), and molecular chaperones in negative feedback loops.
为了茁壮成长并发挥其功能，细胞需要在面对不利的环境条件或在分化过程中对蛋白质组进行彻底重构时，维持蛋白质组的平衡。在蛋白质组平衡调控的核心是一种古老的转录机制，即所谓的热休克反应（HSR），它由所有真核细胞中的热休克转录因子 1（Hsf1）协调。由于 Hsf1 与衰老以及癌症和神经退行性疾病等几种病理学有关，因此了解 Hsf1 的调控可能会开辟新的治疗机会。在这篇综述中，我们讨论了通过涉及 Hsf1 合成和降解、构象重排和翻译后修饰（PTMs）以及负反馈回路中的分子伴侣的多个控制回路来调节 Hsf1 的转录活性。
