Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit
In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the cen...
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2013
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| Online Access: | http://hdl.handle.net/1721.1/77232 https://orcid.org/0000-0001-9837-0314 |
| _version_ | 1826192003235315712 |
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| author | Rock, Jeremy Michael Amon, Angelika B |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rock, Jeremy Michael Amon, Angelika B |
| author_sort | Rock, Jeremy Michael |
| collection | MIT |
| description | In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning. |
| first_indexed | 2024-09-23T09:04:41Z |
| format | Article |
| id | mit-1721.1/77232 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:04:41Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/772322022-09-30T13:15:57Z Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit Rock, Jeremy Michael Amon, Angelika B Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Amon, Angelika Rock, Jeremy Michael Amon, Angelika B. In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning. National Institutes of Health (U.S.) (GM056800) National Science Foundation (U.S.). Predoctoral Fellowship 2013-02-28T15:50:53Z 2013-02-28T15:50:53Z 2011-02 2011-06 Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/77232 Rock, J. M., and A. Amon. “Cdc15 Integrates Tem1 GTPase-mediated Spatial Signals with Polo Kinase-mediated Temporal Cues to Activate Mitotic Exit.” Genes & Development 25.18 (2011): 1943–1954. https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1101/gad.17257711 Genes and Development Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Cold Spring Harbor Laboratory Press Amon via Jennifer Cimino |
| spellingShingle | Rock, Jeremy Michael Amon, Angelika B Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title | Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title_full | Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title_fullStr | Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title_full_unstemmed | Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title_short | Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit |
| title_sort | cdc15 integrates tem1 gtpase mediated spatial signals with polo kinase mediated temporal cues to activate mitotic exit |
| url | http://hdl.handle.net/1721.1/77232 https://orcid.org/0000-0001-9837-0314 |
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