A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast
Mitotic exit is a critical cell cycle transition that requires the careful coordination of nuclear positioning and cyclin B destruction in budding yeast for the maintenance of genome integrity. The mitotic exit network (MEN) is a Ras-like signal transduction pathway that promotes this process during...
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MDPI AG
2021-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/46 |
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| author | Michael Vannini Victoria R. Mingione Ashleigh Meyer Courtney Sniffen Jenna Whalen Anupama Seshan |
| author_facet | Michael Vannini Victoria R. Mingione Ashleigh Meyer Courtney Sniffen Jenna Whalen Anupama Seshan |
| author_sort | Michael Vannini |
| collection | DOAJ |
| description | Mitotic exit is a critical cell cycle transition that requires the careful coordination of nuclear positioning and cyclin B destruction in budding yeast for the maintenance of genome integrity. The mitotic exit network (MEN) is a Ras-like signal transduction pathway that promotes this process during anaphase. A crucial step in MEN activation occurs when the Dbf2-Mob1 protein kinase complex associates with the Nud1 scaffold protein at the yeast spindle pole bodies (SPBs; centrosome equivalents) and thereby becomes activated. This requires prior priming phosphorylation of Nud1 by Cdc15 at SPBs. Cdc15 activation, in turn, requires both the Tem1 GTPase and the Polo kinase Cdc5, but how Cdc15 associates with SPBs is not well understood. We have identified a hyperactive allele of <i>NUD1</i>, <i>nud1-A308T</i>, that recruits Cdc15 to SPBs in all stages of the cell cycle in a <i>CDC5</i>-independent manner. This allele leads to early recruitment of Dbf2-Mob1 during metaphase and requires known Cdc15 phospho-sites on Nud1. The presence of <i>nud1-A308T</i> leads to loss of coupling between nuclear position and mitotic exit in cells with mispositioned spindles. Our findings highlight the importance of scaffold regulation in signaling pathways to prevent improper activation. |
| first_indexed | 2024-03-10T03:46:31Z |
| format | Article |
| id | doaj.art-8a0131c555504f668db5c1c01d17849d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:46:31Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8a0131c555504f668db5c1c01d17849d2023-11-23T11:19:22ZengMDPI AGCells2073-44092021-12-011114610.3390/cells11010046A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding YeastMichael Vannini0Victoria R. Mingione1Ashleigh Meyer2Courtney Sniffen3Jenna Whalen4Anupama Seshan5Boston University School of Medicine, Boston, MA 02118, USADepartment of Pharmacological Sciences, Stony Brook University School of Medicine, Stony Brook, NY 11794, USADana Farber Cancer Institute, Boston, MA 02215, USARenaissance School of Medicine, Stony Brook University Hospital, Stony Brook, NY 11794, USADepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USADepartment of Biology, Emmanuel College, Boston, MA 02115, USAMitotic exit is a critical cell cycle transition that requires the careful coordination of nuclear positioning and cyclin B destruction in budding yeast for the maintenance of genome integrity. The mitotic exit network (MEN) is a Ras-like signal transduction pathway that promotes this process during anaphase. A crucial step in MEN activation occurs when the Dbf2-Mob1 protein kinase complex associates with the Nud1 scaffold protein at the yeast spindle pole bodies (SPBs; centrosome equivalents) and thereby becomes activated. This requires prior priming phosphorylation of Nud1 by Cdc15 at SPBs. Cdc15 activation, in turn, requires both the Tem1 GTPase and the Polo kinase Cdc5, but how Cdc15 associates with SPBs is not well understood. We have identified a hyperactive allele of <i>NUD1</i>, <i>nud1-A308T</i>, that recruits Cdc15 to SPBs in all stages of the cell cycle in a <i>CDC5</i>-independent manner. This allele leads to early recruitment of Dbf2-Mob1 during metaphase and requires known Cdc15 phospho-sites on Nud1. The presence of <i>nud1-A308T</i> leads to loss of coupling between nuclear position and mitotic exit in cells with mispositioned spindles. Our findings highlight the importance of scaffold regulation in signaling pathways to prevent improper activation.https://www.mdpi.com/2073-4409/11/1/46Nud1Cdc15MENmitotic exitDbf2Mob1 |
| spellingShingle | Michael Vannini Victoria R. Mingione Ashleigh Meyer Courtney Sniffen Jenna Whalen Anupama Seshan A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast Cells Nud1 Cdc15 MEN mitotic exit Dbf2 Mob1 |
| title | A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast |
| title_full | A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast |
| title_fullStr | A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast |
| title_full_unstemmed | A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast |
| title_short | A Novel Hyperactive Nud1 Mitotic Exit Network Scaffold Causes Spindle Position Checkpoint Bypass in Budding Yeast |
| title_sort | novel hyperactive nud1 mitotic exit network scaffold causes spindle position checkpoint bypass in budding yeast |
| topic | Nud1 Cdc15 MEN mitotic exit Dbf2 Mob1 |
| url | https://www.mdpi.com/2073-4409/11/1/46 |
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