The BRCT domains of ECT2 have distinct functions during cytokinesis
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
During cell division, the guanine nucleotide exchange factor (GEF) ECT2 activates RhoA in a narrow zone at the cell equator in anaphase. ECT2 consists of three BRCT domains (BRCT0, 1, and 2), a catalytic GEF, and a pleckstrin homology (PH) domain. How the conserved BRCT domains spatially and temporally control ECT2 activity remains unclear. We reveal that each BRCT domain makes distinct contributions to the ECT2 function. We find that BRCT0 contributes to, and BRCT1 is essential for, ECT2 activation in anaphase. BRCT2 integrates two functions: GEF inhibition and RACGAP1 binding, which together limit ECT2 activity to a narrow zone at the cell equator. BRCT2-dependent control of active RhoA zone dimension functions in addition to the inhibitory signal of the astral microtubules. Our analysis provides detailed mechanistic insights into how ECT2 activity is regulated and how that regulation ensures, together with other signaling pathways, successful cell division.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Cell reports - 34(2021), 9 vom: 02. März, Seite 108805 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schneid, Sandra [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2022 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2021.108805 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322148529 |
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| 100 | 1 | |a Schneid, Sandra |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The BRCT domains of ECT2 have distinct functions during cytokinesis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 25.01.2022 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a During cell division, the guanine nucleotide exchange factor (GEF) ECT2 activates RhoA in a narrow zone at the cell equator in anaphase. ECT2 consists of three BRCT domains (BRCT0, 1, and 2), a catalytic GEF, and a pleckstrin homology (PH) domain. How the conserved BRCT domains spatially and temporally control ECT2 activity remains unclear. We reveal that each BRCT domain makes distinct contributions to the ECT2 function. We find that BRCT0 contributes to, and BRCT1 is essential for, ECT2 activation in anaphase. BRCT2 integrates two functions: GEF inhibition and RACGAP1 binding, which together limit ECT2 activity to a narrow zone at the cell equator. BRCT2-dependent control of active RhoA zone dimension functions in addition to the inhibitory signal of the astral microtubules. Our analysis provides detailed mechanistic insights into how ECT2 activity is regulated and how that regulation ensures, together with other signaling pathways, successful cell division | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Video-Audio Media | |
| 650 | 4 | |a BRCT domain | |
| 650 | 4 | |a Cyk4 | |
| 650 | 4 | |a ECT2 | |
| 650 | 4 | |a PLK1 | |
| 650 | 4 | |a RACGAP1 | |
| 650 | 4 | |a RhoA | |
| 650 | 4 | |a cell division | |
| 650 | 4 | |a cytokinesis | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a ECT2 protein, human |2 NLM | |
| 650 | 7 | |a GTPase-Activating Proteins |2 NLM | |
| 650 | 7 | |a Guanine Nucleotide Exchange Factors |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a SLC2A4RG protein, human |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a mgcRacGAP |2 NLM | |
| 650 | 7 | |a RHOA protein, human |2 NLM | |
| 650 | 7 | |a 124671-05-2 |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a rhoA GTP-Binding Protein |2 NLM | |
| 650 | 7 | |a EC 3.6.5.2 |2 NLM | |
| 700 | 1 | |a Wolff, Friederike |e verfasserin |4 aut | |
| 700 | 1 | |a Buchner, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Bertram, Nils |e verfasserin |4 aut | |
| 700 | 1 | |a Baygün, Seren |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa, Pedro |e verfasserin |4 aut | |
| 700 | 1 | |a Mangal, Sriyash |e verfasserin |4 aut | |
| 700 | 1 | |a Zanin, Esther |e verfasserin |4 aut | |
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