Cross-compartment signal propagation in the mitotic exit network
In budding yeast, the mitotic exit network (MEN), a GTPase signaling cascade, integrates spatial and temporal cues to promote exit from mitosis. This signal integration requires transmission of a signal generated on the cytoplasmic face of spindle pole bodies (SPBs; yeast equivalent of centrosomes)...
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eLife Sciences Publications Ltd
2021-01-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/63645 |
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author | Xiaoxue Zhou Wenxue Li Yansheng Liu Angelika Amon |
author_facet | Xiaoxue Zhou Wenxue Li Yansheng Liu Angelika Amon |
author_sort | Xiaoxue Zhou |
collection | DOAJ |
description | In budding yeast, the mitotic exit network (MEN), a GTPase signaling cascade, integrates spatial and temporal cues to promote exit from mitosis. This signal integration requires transmission of a signal generated on the cytoplasmic face of spindle pole bodies (SPBs; yeast equivalent of centrosomes) to the nucleolus, where the MEN effector protein Cdc14 resides. Here, we show that the MEN activating signal at SPBs is relayed to Cdc14 in the nucleolus through the dynamic localization of its terminal kinase complex Dbf2-Mob1. Cdc15, the protein kinase that activates Dbf2-Mob1 at SPBs, also regulates its nuclear access. Once in the nucleus, priming phosphorylation of Cfi1/Net1, the nucleolar anchor of Cdc14, by the Polo-like kinase Cdc5 targets Dbf2-Mob1 to the nucleolus. Nucleolar Dbf2-Mob1 then phosphorylates Cfi1/Net1 and Cdc14, activating Cdc14. The kinase-primed transmission of the MEN signal from the cytoplasm to the nucleolus exemplifies how signaling cascades can bridge distant inputs and responses. |
first_indexed | 2024-04-11T08:59:44Z |
format | Article |
id | doaj.art-ac42a4f10b734bc3bacff12a2e48608d |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T08:59:44Z |
publishDate | 2021-01-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-ac42a4f10b734bc3bacff12a2e48608d2022-12-22T04:32:49ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.63645Cross-compartment signal propagation in the mitotic exit networkXiaoxue Zhou0https://orcid.org/0000-0002-4551-0608Wenxue Li1Yansheng Liu2https://orcid.org/0000-0002-2626-3912Angelika Amon3https://orcid.org/0000-0001-9837-0314David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United StatesYale Cancer Biology Institute, Department of Pharmacology, Yale University, West Haven, United StatesYale Cancer Biology Institute, Department of Pharmacology, Yale University, West Haven, United StatesDavid H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United StatesIn budding yeast, the mitotic exit network (MEN), a GTPase signaling cascade, integrates spatial and temporal cues to promote exit from mitosis. This signal integration requires transmission of a signal generated on the cytoplasmic face of spindle pole bodies (SPBs; yeast equivalent of centrosomes) to the nucleolus, where the MEN effector protein Cdc14 resides. Here, we show that the MEN activating signal at SPBs is relayed to Cdc14 in the nucleolus through the dynamic localization of its terminal kinase complex Dbf2-Mob1. Cdc15, the protein kinase that activates Dbf2-Mob1 at SPBs, also regulates its nuclear access. Once in the nucleus, priming phosphorylation of Cfi1/Net1, the nucleolar anchor of Cdc14, by the Polo-like kinase Cdc5 targets Dbf2-Mob1 to the nucleolus. Nucleolar Dbf2-Mob1 then phosphorylates Cfi1/Net1 and Cdc14, activating Cdc14. The kinase-primed transmission of the MEN signal from the cytoplasm to the nucleolus exemplifies how signaling cascades can bridge distant inputs and responses.https://elifesciences.org/articles/63645mitotic exit networkcell cyclesignal transduction |
spellingShingle | Xiaoxue Zhou Wenxue Li Yansheng Liu Angelika Amon Cross-compartment signal propagation in the mitotic exit network eLife mitotic exit network cell cycle signal transduction |
title | Cross-compartment signal propagation in the mitotic exit network |
title_full | Cross-compartment signal propagation in the mitotic exit network |
title_fullStr | Cross-compartment signal propagation in the mitotic exit network |
title_full_unstemmed | Cross-compartment signal propagation in the mitotic exit network |
title_short | Cross-compartment signal propagation in the mitotic exit network |
title_sort | cross compartment signal propagation in the mitotic exit network |
topic | mitotic exit network cell cycle signal transduction |
url | https://elifesciences.org/articles/63645 |
work_keys_str_mv | AT xiaoxuezhou crosscompartmentsignalpropagationinthemitoticexitnetwork AT wenxueli crosscompartmentsignalpropagationinthemitoticexitnetwork AT yanshengliu crosscompartmentsignalpropagationinthemitoticexitnetwork AT angelikaamon crosscompartmentsignalpropagationinthemitoticexitnetwork |