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Protein Condensates with Appropriate Material Properties Regulate Tumorigenesis

Wei Li, Jing Hu, Bi Shi, Hao Jiang
doi: https://doi.org/10.1101/536839
Wei Li
1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham School of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine
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Jing Hu
1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham School of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine
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Bi Shi
1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham School of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine
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Hao Jiang
1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham School of Medicine, Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine
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  • For correspondence: hj8d@virginia.edu
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ABSTRACT

It remains unknown if material properties of biomolecular condensates regulate cancer. Here we show that AKAP95, a nuclear protein that regulates transcription and RNA splicing, plays an important role in tumorigenesis by promoting cancer cell growth and suppressing oncogene-induced senescence. We show that AKAP95 forms phase-separated and liquid-like condensates in vitro and in nucleus. Mutations of key residues to different amino acids perturb AKAP95 condensation in opposite directions. Importantly, the activity of AKAP95 in splice regulation is abolished by disruption of condensation, significantly impaired by hardening of condensates, and regained by substituting its condensation-mediating region with other condensation-mediating regions from irrelevant proteins. Moreover, the abilities of AKAP95 in regulating gene expression and promoting tumorigenesis require AKAP95 to form condensates with proper liquidity and dynamicity. These results thus link phase separation to tumorigenesis and uncover an important role of appropriate material properties of protein condensates in gene regulation and cancer.

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  • The authors have declared that no conflict of interest exists.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 18, 2019.
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Protein Condensates with Appropriate Material Properties Regulate Tumorigenesis
Wei Li, Jing Hu, Bi Shi, Hao Jiang
bioRxiv 536839; doi: https://doi.org/10.1101/536839
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Protein Condensates with Appropriate Material Properties Regulate Tumorigenesis
Wei Li, Jing Hu, Bi Shi, Hao Jiang
bioRxiv 536839; doi: https://doi.org/10.1101/536839

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