MYO10 regulates genome stability and cancer inflammation through mediating mitosis
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Genomic instability can promote inflammation and tumor development. Previous research revealed an unexpected layer of regulation of genomic instability by a cytoplasmic protein MYO10; however, the underlying mechanism remained unclear. Here, we report a protein stability-mediated mitotic regulation of MYO10 in controlling genome stability. We characterized a degron motif and phosphorylation residues in the degron that mediate β-TrCP1-dependent MYO10 degradation. The level of phosphorylated MYO10 protein transiently increases during mitosis, which is accompanied by a spatiotemporal cellular localization change first accumulating at the centrosome then at the midbody. Depletion of MYO10 or expression of MYO10 degron mutants, including those found in cancer patients, disrupts mitosis, increases genomic instability and inflammation, and promotes tumor growth; however, they also increase the sensitivity of cancer cells to Taxol. Our studies demonstrate a critical role of MYO10 in mitosis progression, through which it regulates genome stability, cancer growth, and cellular response to mitotic toxins.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 5 vom: 30. Mai, Seite 112531 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mayca Pozo, Franklin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 01.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112531 |
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| funding: |
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| 520 | |a Genomic instability can promote inflammation and tumor development. Previous research revealed an unexpected layer of regulation of genomic instability by a cytoplasmic protein MYO10; however, the underlying mechanism remained unclear. Here, we report a protein stability-mediated mitotic regulation of MYO10 in controlling genome stability. We characterized a degron motif and phosphorylation residues in the degron that mediate β-TrCP1-dependent MYO10 degradation. The level of phosphorylated MYO10 protein transiently increases during mitosis, which is accompanied by a spatiotemporal cellular localization change first accumulating at the centrosome then at the midbody. Depletion of MYO10 or expression of MYO10 degron mutants, including those found in cancer patients, disrupts mitosis, increases genomic instability and inflammation, and promotes tumor growth; however, they also increase the sensitivity of cancer cells to Taxol. Our studies demonstrate a critical role of MYO10 in mitosis progression, through which it regulates genome stability, cancer growth, and cellular response to mitotic toxins | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CP: Molecular biology | |
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| 650 | 4 | |a Taxol sensitivity | |
| 650 | 4 | |a cancer inflammation | |
| 650 | 4 | |a cancer mutation | |
| 650 | 4 | |a degron | |
| 650 | 4 | |a genomic instability | |
| 650 | 4 | |a phosphorylation | |
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| 700 | 1 | |a Geng, Xinran |e verfasserin |4 aut | |
| 700 | 1 | |a Miyagi, Masaru |e verfasserin |4 aut | |
| 700 | 1 | |a Amin, Amanda L |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Alex Y |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Youwei |e verfasserin |4 aut | |
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