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)...

Full description

Bibliographic Details
Main Authors: Xiaoxue Zhou, Wenxue Li, Yansheng Liu, Angelika Amon
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/63645
_version_ 1797991905977434112
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
record_format Article
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