An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component
Intrinsically disordered proteins play causative roles in many human diseases. Their overexpression is toxic in many organisms, but the causes of toxicity are opaque. In this paper, we exploit yeast technologies to determine the root of toxicity for one such protein, the yeast prion Rnq1. This prote...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Rockefeller University Press, The
2012
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| Online Access: | http://hdl.handle.net/1721.1/71750 https://orcid.org/0000-0003-1307-882X |
| _version_ | 1826211187850739712 |
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| author | Treusch, Sebastian Lindquist, Susan |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Treusch, Sebastian Lindquist, Susan |
| author_sort | Treusch, Sebastian |
| collection | MIT |
| description | Intrinsically disordered proteins play causative roles in many human diseases. Their overexpression is toxic in many organisms, but the causes of toxicity are opaque. In this paper, we exploit yeast technologies to determine the root of toxicity for one such protein, the yeast prion Rnq1. This protein is profoundly toxic when overexpressed but only in cells carrying the endogenous Rnq1 protein in its [RNQ[superscript +]] prion (amyloid) conformation. Surprisingly, toxicity was not caused by general proteotoxic stress. Rather, it involved a highly specific mitotic arrest mediated by the Mad2 cell cycle checkpoint. Monopolar spindles accumulated as a result of defective duplication of the yeast centrosome (spindle pole body [SPB]). This arose from selective Rnq1-mediated sequestration of the core SPB component Spc42 in the insoluble protein deposit (IPOD). Rnq1 does not normally participate in spindle pole dynamics, but it does assemble at the IPOD when aggregated. Our work illustrates how the promiscuous interactions of an intrinsically disordered protein can produce highly specific cellular toxicities through illicit, yet highly specific, interactions with the proteome. |
| first_indexed | 2024-09-23T15:01:58Z |
| format | Article |
| id | mit-1721.1/71750 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:01:58Z |
| publishDate | 2012 |
| publisher | Rockefeller University Press, The |
| record_format | dspace |
| spelling | mit-1721.1/717502022-10-02T00:06:31Z An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component Treusch, Sebastian Lindquist, Susan Massachusetts Institute of Technology. Department of Biology Lindquist, Susan Treusch, Sebastian Lindquist, Susan Intrinsically disordered proteins play causative roles in many human diseases. Their overexpression is toxic in many organisms, but the causes of toxicity are opaque. In this paper, we exploit yeast technologies to determine the root of toxicity for one such protein, the yeast prion Rnq1. This protein is profoundly toxic when overexpressed but only in cells carrying the endogenous Rnq1 protein in its [RNQ[superscript +]] prion (amyloid) conformation. Surprisingly, toxicity was not caused by general proteotoxic stress. Rather, it involved a highly specific mitotic arrest mediated by the Mad2 cell cycle checkpoint. Monopolar spindles accumulated as a result of defective duplication of the yeast centrosome (spindle pole body [SPB]). This arose from selective Rnq1-mediated sequestration of the core SPB component Spc42 in the insoluble protein deposit (IPOD). Rnq1 does not normally participate in spindle pole dynamics, but it does assemble at the IPOD when aggregated. Our work illustrates how the promiscuous interactions of an intrinsically disordered protein can produce highly specific cellular toxicities through illicit, yet highly specific, interactions with the proteome. 2012-07-23T15:38:26Z 2012-07-23T15:38:26Z 2012-04 2011-08 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/71750 Treusch, S., and S. Lindquist. “An Intrinsically Disordered Yeast Prion Arrests the Cell Cycle by Sequestering a Spindle Pole Body Component.” The Journal of Cell Biology 197.3 (2012): 369–379. Copyright © 2012 by The Rockefeller University Press https://orcid.org/0000-0003-1307-882X en_US http://dx.doi.org/10.1083/jcb.201108146 Journal of Cell Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press, The Rockefeller UP |
| spellingShingle | Treusch, Sebastian Lindquist, Susan An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title | An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title_full | An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title_fullStr | An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title_full_unstemmed | An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title_short | An intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| title_sort | intrinsically disordered yeast prion arrests the cell cycle by sequestering a spindle pole body component |
| url | http://hdl.handle.net/1721.1/71750 https://orcid.org/0000-0003-1307-882X |
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