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由液泡/溶酶体中依赖细胞周期蛋白依赖性激酶的PI3,5P信号介导的对压力的早期保护。

Early protection to stress mediated by CDK-dependent PI3,5P signaling from the vacuole/lysosome.

作者信息

Jin Natsuko, Jin Yui, Weisman Lois S

机构信息

Life Sciences Institute, University of Michigan, Ann Arbor, MI.

Life Sciences Institute, University of Michigan, Ann Arbor, MI

出版信息

J Cell Biol. 2017 Jul 3;216(7):2075-2090. doi: 10.1083/jcb.201611144. Epub 2017 Jun 21.

DOI:10.1083/jcb.201611144
PMID:28637746
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5496620/
Abstract

Adaptation to environmental stress is critical for cell survival. Adaptation generally occurs via changes in transcription and translation. However, there is a time lag before changes in gene expression, which suggests that more rapid mechanisms likely exist. In this study, we show that in yeast, the cyclin-dependent kinase Pho85/CDK5 provides protection against hyperosmotic stress and acts before long-term adaptation provided by Hog1. This protection requires the vacuolar/endolysosomal signaling lipid PI3,5P We show that Pho85/CDK5 directly phosphorylates and positively regulates the PI3P-5 kinase Fab1/PIKfyve complex and provide evidence that this regulation is conserved in mammalian cells. Moreover, this regulation is particularly crucial in yeast for the stress-induced transient elevation of PI3,5P Our study reveals a rapid protection mechanism regulated by Pho85/CDK5 via signaling from the vacuole/lysosome, which is distinct temporally and spatially from the previously discovered long-term adaptation Hog1 pathway, which signals from the nucleus.

摘要

适应环境压力对细胞存活至关重要。适应通常通过转录和翻译的变化来发生。然而，基因表达变化之前存在时间滞后，这表明可能存在更快速的机制。在本研究中，我们表明在酵母中，细胞周期蛋白依赖性激酶Pho85/CDK5提供针对高渗应激的保护，并在Hog1提供的长期适应之前发挥作用。这种保护需要液泡/内溶酶体信号脂质PI3,5P。我们表明Pho85/CDK5直接磷酸化并正向调节PI3P-5激酶Fab1/PIKfyve复合物，并提供证据表明这种调节在哺乳动物细胞中是保守的。此外，这种调节在酵母中对于应激诱导的PI3,5P瞬时升高尤为关键。我们的研究揭示了一种由Pho85/CDK5通过液泡/溶酶体信号传导调节的快速保护机制，其在时间和空间上与先前发现的从细胞核发出信号的长期适应Hog1途径不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/1ba8099f8686/JCB_201611144_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/f7ea49e5796c/JCB_201611144_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/5a17a7ddfa4d/JCB_201611144_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/abb8252cf1a1/JCB_201611144_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/b5a68b86b15e/JCB_201611144_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/b3e25fab83b3/JCB_201611144_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/7282037527e0/JCB_201611144_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/57dae92db5fb/JCB_201611144_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/ee634f3f87ec/JCB_201611144_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/6ad4b6e46ed7/JCB_201611144_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/1ba8099f8686/JCB_201611144_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/f7ea49e5796c/JCB_201611144_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/5a17a7ddfa4d/JCB_201611144_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/abb8252cf1a1/JCB_201611144_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/b5a68b86b15e/JCB_201611144_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/b3e25fab83b3/JCB_201611144_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/7282037527e0/JCB_201611144_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/57dae92db5fb/JCB_201611144_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/ee634f3f87ec/JCB_201611144_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/6ad4b6e46ed7/JCB_201611144_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e524/5496620/1ba8099f8686/JCB_201611144_Fig10.jpg

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