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Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes

OBJECTIVE: Miscarriages affect 10% of women aged 25–29, and 53% of women over 45. The primary cause of miscarriage is aneuploidy that originated in eggs. The Aurora kinase family has three members that regulate chromosome segregation. Therefore, distinguishing the roles of these isoforms is importan...

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Autores principales: Kratka, Caroline, Drutovic, David, Blengini, Cecilia S., Schindler, Karen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900367/
https://www.ncbi.nlm.nih.gov/pubmed/35255953
http://dx.doi.org/10.1186/s13104-022-05987-4
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author Kratka, Caroline
Drutovic, David
Blengini, Cecilia S.
Schindler, Karen
author_facet Kratka, Caroline
Drutovic, David
Blengini, Cecilia S.
Schindler, Karen
author_sort Kratka, Caroline
collection PubMed
description OBJECTIVE: Miscarriages affect 10% of women aged 25–29, and 53% of women over 45. The primary cause of miscarriage is aneuploidy that originated in eggs. The Aurora kinase family has three members that regulate chromosome segregation. Therefore, distinguishing the roles of these isoforms is important to understand aneuploidy etiology. In meiosis, Aurora kinase A (AURKA) localizes to spindle poles, where it binds TPX2. Aurora kinase C (AURKC) localizes on chromosomes, where it replaces AURKB as the primary AURK in the chromosomal passenger complex (CPC) via INCENP binding. Although AURKA compensates for CPC function in oocytes lacking AURKB/C, it is unknown whether AURKA binds INCENP in wild type mouse oocytes. ZINC08918027 (ZC) is an inhibitor that prevents the interaction between AURKB and INCENP in mitotic cells. We hypothesized that ZC would block CPC function of any AURK isoform. RESULTS: ZC treatment caused defects in meiotic progression and spindle building. By Western blotting and immunofluorescence, we observed that activated AURKA and AURKC levels in ZC-treated oocytes decreased compared to controls. These results suggest there is a population of AURKA-CPC in mouse oocytes. These data together suggest that INCENP-dependent AURKA and AURKC activities are needed for spindle bipolarity and meiotic progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-022-05987-4.
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spelling pubmed-89003672022-03-17 Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes Kratka, Caroline Drutovic, David Blengini, Cecilia S. Schindler, Karen BMC Res Notes Research Note OBJECTIVE: Miscarriages affect 10% of women aged 25–29, and 53% of women over 45. The primary cause of miscarriage is aneuploidy that originated in eggs. The Aurora kinase family has three members that regulate chromosome segregation. Therefore, distinguishing the roles of these isoforms is important to understand aneuploidy etiology. In meiosis, Aurora kinase A (AURKA) localizes to spindle poles, where it binds TPX2. Aurora kinase C (AURKC) localizes on chromosomes, where it replaces AURKB as the primary AURK in the chromosomal passenger complex (CPC) via INCENP binding. Although AURKA compensates for CPC function in oocytes lacking AURKB/C, it is unknown whether AURKA binds INCENP in wild type mouse oocytes. ZINC08918027 (ZC) is an inhibitor that prevents the interaction between AURKB and INCENP in mitotic cells. We hypothesized that ZC would block CPC function of any AURK isoform. RESULTS: ZC treatment caused defects in meiotic progression and spindle building. By Western blotting and immunofluorescence, we observed that activated AURKA and AURKC levels in ZC-treated oocytes decreased compared to controls. These results suggest there is a population of AURKA-CPC in mouse oocytes. These data together suggest that INCENP-dependent AURKA and AURKC activities are needed for spindle bipolarity and meiotic progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-022-05987-4. BioMed Central 2022-03-07 /pmc/articles/PMC8900367/ /pubmed/35255953 http://dx.doi.org/10.1186/s13104-022-05987-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Note
Kratka, Caroline
Drutovic, David
Blengini, Cecilia S.
Schindler, Karen
Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title_full Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title_fullStr Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title_full_unstemmed Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title_short Using ZINC08918027 inhibitor to determine Aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
title_sort using zinc08918027 inhibitor to determine aurora kinase-chromosomal passenger complex isoforms in mouse oocytes
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900367/
https://www.ncbi.nlm.nih.gov/pubmed/35255953
http://dx.doi.org/10.1186/s13104-022-05987-4
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