Cargando…
ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity
In both mitosis and meiosis, metaphase to anaphase transition requires the activity of a ubiquitin ligase known as anaphase promoting complex/cyclosome (APC/C). The activation of APC/C in metaphase is under the control of the checkpoint mechanism, called the spindle assembly checkpoint (SAC), which...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770151/ https://www.ncbi.nlm.nih.gov/pubmed/31540287 http://dx.doi.org/10.3390/ijms20184537 |
_version_ | 1783455404376719360 |
---|---|
author | Radonova, Lenka Svobodova, Tereza Skultety, Michal Mrkva, Ondrej Libichova, Lenka Stein, Paula Anger, Martin |
author_facet | Radonova, Lenka Svobodova, Tereza Skultety, Michal Mrkva, Ondrej Libichova, Lenka Stein, Paula Anger, Martin |
author_sort | Radonova, Lenka |
collection | PubMed |
description | In both mitosis and meiosis, metaphase to anaphase transition requires the activity of a ubiquitin ligase known as anaphase promoting complex/cyclosome (APC/C). The activation of APC/C in metaphase is under the control of the checkpoint mechanism, called the spindle assembly checkpoint (SAC), which monitors the correct attachment of all kinetochores to the spindle. It has been shown previously in somatic cells that exposure to a small molecule inhibitor, prodrug tosyl-l-arginine methyl ester (proTAME), resulted in cell cycle arrest in metaphase, with low APC/C activity. Interestingly, some reports have also suggested that the activity of SAC is required for this arrest. We focused on the characterization of proTAME inhibition of cell cycle progression in mammalian oocytes and embryos. Our results show that mammalian oocytes and early cleavage embryos show dose-dependent metaphase arrest after exposure to proTAME. However, in comparison to the somatic cells, we show here that the proTAME-induced arrest in these cells does not require SAC activity. Our results revealed important differences between mammalian oocytes and early embryos and somatic cells in their requirements of SAC for APC/C inhibition. In comparison to the somatic cells, oocytes and embryos show much higher frequency of aneuploidy. Our results are therefore important for understanding chromosome segregation control mechanisms, which might contribute to the premature termination of development or severe developmental and mental disorders of newborns. |
format | Online Article Text |
id | pubmed-6770151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67701512019-10-30 ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity Radonova, Lenka Svobodova, Tereza Skultety, Michal Mrkva, Ondrej Libichova, Lenka Stein, Paula Anger, Martin Int J Mol Sci Article In both mitosis and meiosis, metaphase to anaphase transition requires the activity of a ubiquitin ligase known as anaphase promoting complex/cyclosome (APC/C). The activation of APC/C in metaphase is under the control of the checkpoint mechanism, called the spindle assembly checkpoint (SAC), which monitors the correct attachment of all kinetochores to the spindle. It has been shown previously in somatic cells that exposure to a small molecule inhibitor, prodrug tosyl-l-arginine methyl ester (proTAME), resulted in cell cycle arrest in metaphase, with low APC/C activity. Interestingly, some reports have also suggested that the activity of SAC is required for this arrest. We focused on the characterization of proTAME inhibition of cell cycle progression in mammalian oocytes and embryos. Our results show that mammalian oocytes and early cleavage embryos show dose-dependent metaphase arrest after exposure to proTAME. However, in comparison to the somatic cells, we show here that the proTAME-induced arrest in these cells does not require SAC activity. Our results revealed important differences between mammalian oocytes and early embryos and somatic cells in their requirements of SAC for APC/C inhibition. In comparison to the somatic cells, oocytes and embryos show much higher frequency of aneuploidy. Our results are therefore important for understanding chromosome segregation control mechanisms, which might contribute to the premature termination of development or severe developmental and mental disorders of newborns. MDPI 2019-09-13 /pmc/articles/PMC6770151/ /pubmed/31540287 http://dx.doi.org/10.3390/ijms20184537 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Radonova, Lenka Svobodova, Tereza Skultety, Michal Mrkva, Ondrej Libichova, Lenka Stein, Paula Anger, Martin ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title | ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title_full | ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title_fullStr | ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title_full_unstemmed | ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title_short | ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity |
title_sort | protame arrest in mammalian oocytes and embryos does not require spindle assembly checkpoint activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770151/ https://www.ncbi.nlm.nih.gov/pubmed/31540287 http://dx.doi.org/10.3390/ijms20184537 |
work_keys_str_mv | AT radonovalenka protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT svobodovatereza protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT skultetymichal protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT mrkvaondrej protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT libichovalenka protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT steinpaula protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity AT angermartin protamearrestinmammalianoocytesandembryosdoesnotrequirespindleassemblycheckpointactivity |