Actin remodelling controls proteasome homeostasis upon stress.

Actin remodelling controls proteasome homeostasis upon stress.
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肌动蛋白重塑控制蛋白酶体稳态后的压力。

DOI:
10.1038/s41556-022-00938-4
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发表时间:
2022-07
影响因子:
21.3
通讯作者:
--
中科院分区:
生物学1区
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当细胞受到应激时,大量翻译通常会下调以减少能量需求,而应激反应蛋白质则同时上调。为了促进蛋白酶体组装和活性并在TORC 1抑制后维持细胞活力,19S调节颗粒组装分子伴侣(RPAC)被选择性地翻译。然而,这种选择性翻译上调的分子机制尚不清楚。在这里,使用酵母,我们发现肌动蛋白细胞骨架的重塑是重要的RPAC翻译后TORC 1抑制。RPAC ADC 17的mRNA与肌动蛋白电缆相关,并在应激下富集于皮质肌动蛋白斑块,依赖于早期内吞蛋白Ede 1。在TORC 1抑制后,ede1细胞不能诱导RPAC和蛋白酶体组装。相反,人工拴ADC17 mRNA皮质肌动蛋白补丁增强其翻译后的压力。这些研究结果表明,肌动蛋白密集的结构,如皮质肌动蛋白补丁可能作为一个翻译平台的一个子集的压力诱导的mRNA,包括调节蛋白酶体稳态。威廉姆斯等人报道,在酵母中抑制TORC 1后,伴侣蛋白ADC 17的mRNA定位于皮质肌动蛋白斑,在那里其翻译在应激时增强。
When cells are stressed, bulk translation is often downregulated to reduce energy demands while stress-response proteins are simultaneously upregulated. To promote proteasome assembly and activity and maintain cell viability upon TORC1 inhibition, 19S regulatory-particle assembly chaperones (RPACs) are selectively translated. However, the molecular mechanism for such selective translational upregulation is unclear. Here, using yeast, we discover that remodelling of the actin cytoskeleton is important for RPAC translation following TORC1 inhibition. mRNA of the RPAC ADC17 is associated with actin cables and is enriched at cortical actin patches under stress, dependent upon the early endocytic protein Ede1. ede1∆ cells failed to induce RPACs and proteasome assembly upon TORC1 inhibition. Conversely, artificially tethering ADC17 mRNA to cortical actin patches enhanced its translation upon stress. These findings suggest that actin-dense structures such as cortical actin patches may serve as a translation platform for a subset of stress-induced mRNAs including regulators of proteasome homeostasis. Williams et al. report that, upon TORC1 inhibition in yeast, mRNA of the chaperone protein ADC17 is localized to cortical actin patches where its translation is enhanced upon stress.
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