Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Maruyama, Eri O., Lin, Heng, Chiu, Shang-Yi, Yu, H.-M. Ivy, Porter, George A., Hsu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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
_version_ 1782416373043953664
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
work_keys_str_mv AT maruyamaerio extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment
AT linheng extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment
AT chiushangyi extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment
AT yuhmivy extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment
AT portergeorgea extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment
AT hsuwei extraembryonicbutnotembryonicsumospecificprotease2isrequiredforheartdevelopment