Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus
Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, Sci...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2014
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| Online Access: | http://hdl.handle.net/1721.1/84675 https://orcid.org/0000-0002-8288-7607 |
| _version_ | 1826217761062256640 |
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| author | Gora, Kasia G. Cantin, Amber Joshi, Kamal K. Wohlever, Matthew Lee Perchuk, Barrett Chien, Peter, 1976- Laub, Michael T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gora, Kasia G. Cantin, Amber Joshi, Kamal K. Wohlever, Matthew Lee Perchuk, Barrett Chien, Peter, 1976- Laub, Michael T |
| author_sort | Gora, Kasia G. |
| collection | MIT |
| description | Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division. |
| first_indexed | 2024-09-23T17:08:43Z |
| format | Article |
| id | mit-1721.1/84675 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:08:43Z |
| publishDate | 2014 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/846752022-09-29T23:58:06Z Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus Gora, Kasia G. Cantin, Amber Joshi, Kamal K. Wohlever, Matthew Lee Perchuk, Barrett Chien, Peter, 1976- Laub, Michael T Massachusetts Institute of Technology. Department of Biology Gora, Kasia G. Wohlever, Matthew Lee Perchuk, Barrett Laub, Michael T. Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division. National Science Foundation (U.S.). Graduate Research Fellowship Program National Institutes of Health (U.S.) (Grant 5R01GM082899) 2014-02-07T16:22:39Z 2014-02-07T16:22:39Z 2013-02 Article http://purl.org/eprint/type/JournalArticle 0950382X 1365-2958 http://hdl.handle.net/1721.1/84675 Gora, Kasia G., Amber Cantin, Matthew Wohlever, Kamal K. Joshi, Barrett S. Perchuk, Peter Chien, and Michael T. Laub. “Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus.” Molecular Microbiology 87, no. 6 (March 25, 2013): 1277-1289. https://orcid.org/0000-0002-8288-7607 en_US http://dx.doi.org/10.1111/mmi.12166 Molecular Microbiology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Gora, Kasia G. Cantin, Amber Joshi, Kamal K. Wohlever, Matthew Lee Perchuk, Barrett Chien, Peter, 1976- Laub, Michael T Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title | Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title_full | Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title_fullStr | Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title_full_unstemmed | Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title_short | Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus |
| title_sort | regulated proteolysis of a transcription factor complex is critical to cell cycle progression in caulobacter crescentus |
| url | http://hdl.handle.net/1721.1/84675 https://orcid.org/0000-0002-8288-7607 |
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