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Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development
SUMO-specific protease 2 (SENP2) activities to remove SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestation lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756675/ https://www.ncbi.nlm.nih.gov/pubmed/26883797 http://dx.doi.org/10.1038/srep20999 |
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author | Maruyama, Eri O. Lin, Heng Chiu, Shang-Yi Yu, H.-M. Ivy Porter, George A. Hsu, Wei |
author_facet | Maruyama, Eri O. Lin, Heng Chiu, Shang-Yi Yu, H.-M. Ivy Porter, George A. Hsu, Wei |
author_sort | Maruyama, Eri O. |
collection | PubMed |
description | SUMO-specific protease 2 (SENP2) activities to remove SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestation lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and heart abnormalities. Because of the placental deficiencies, the role of SENP2 in development of the embryonic tissues has not been properly determined. The brain and heart abnormalities may be secondary to placental insufficiency. Here we have created a new mouse strain permitting conditional inactivation of SENP2. Mice homozygous for germline deletion of the conditional allele exhibit trophoblast defects and embryonic abnormalities resembling the global SENP2 knockout. However, tissue-specific disruptions of SENP2 demonstrate its dispensable role in embryogenesis. Placental expression of SENP2 is necessary and sufficient for embryonic heart and brain development. Using a protease deficient model, we further demonstrate the requirement of SENP2-dependent SUMO modification in development of all major trophoblast lineages. SENP2 regulates sumoylation of Mdm2 which controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation, respectively. The differentiation of trophoblasts is also dependent on SENP2-mediated activation of p57(Kip2), a CDK-specific inhibitor required for endoreduplication. |
format | Online Article Text |
id | pubmed-4756675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47566752016-02-25 Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development Maruyama, Eri O. Lin, Heng Chiu, Shang-Yi Yu, H.-M. Ivy Porter, George A. Hsu, Wei Sci Rep Article SUMO-specific protease 2 (SENP2) activities to remove SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestation lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and heart abnormalities. Because of the placental deficiencies, the role of SENP2 in development of the embryonic tissues has not been properly determined. The brain and heart abnormalities may be secondary to placental insufficiency. Here we have created a new mouse strain permitting conditional inactivation of SENP2. Mice homozygous for germline deletion of the conditional allele exhibit trophoblast defects and embryonic abnormalities resembling the global SENP2 knockout. However, tissue-specific disruptions of SENP2 demonstrate its dispensable role in embryogenesis. Placental expression of SENP2 is necessary and sufficient for embryonic heart and brain development. Using a protease deficient model, we further demonstrate the requirement of SENP2-dependent SUMO modification in development of all major trophoblast lineages. SENP2 regulates sumoylation of Mdm2 which controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation, respectively. The differentiation of trophoblasts is also dependent on SENP2-mediated activation of p57(Kip2), a CDK-specific inhibitor required for endoreduplication. Nature Publishing Group 2016-02-17 /pmc/articles/PMC4756675/ /pubmed/26883797 http://dx.doi.org/10.1038/srep20999 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Maruyama, Eri O. Lin, Heng Chiu, Shang-Yi Yu, H.-M. Ivy Porter, George A. Hsu, Wei Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title | Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title_full | Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title_fullStr | Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title_full_unstemmed | Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title_short | Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development |
title_sort | extraembryonic but not embryonic sumo-specific protease 2 is required for heart development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756675/ https://www.ncbi.nlm.nih.gov/pubmed/26883797 http://dx.doi.org/10.1038/srep20999 |
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