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Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics()
Protein phosphatase 1 (PP1) catalyzes more than half of all phosphoserine/threonine dephosphorylation reactions in mammalian cells. In vivo PP1 does not exist as a free catalytic subunit but is always associated with at least one regulatory PP1-interacting protein (PIP) to generate a large set of di...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114192/ https://www.ncbi.nlm.nih.gov/pubmed/30056088 http://dx.doi.org/10.1016/j.bbamcr.2018.07.019 |
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author | Ferreira, Mónica Beullens, Monique Bollen, Mathieu Van Eynde, Aleyde |
author_facet | Ferreira, Mónica Beullens, Monique Bollen, Mathieu Van Eynde, Aleyde |
author_sort | Ferreira, Mónica |
collection | PubMed |
description | Protein phosphatase 1 (PP1) catalyzes more than half of all phosphoserine/threonine dephosphorylation reactions in mammalian cells. In vivo PP1 does not exist as a free catalytic subunit but is always associated with at least one regulatory PP1-interacting protein (PIP) to generate a large set of distinct holoenzymes. Each PP1 complex controls the dephosphorylation of only a small subset of PP1 substrates. We screened the literature for genetically engineered mouse models and identified models for all PP1 isoforms and 104 PIPs. PP1 itself and at least 49 PIPs were connected to human disease-associated phenotypes. Additionally, phenotypes related to 17 PIPs were clearly linked to altered PP1 function, while such information was lacking for 32 other PIPs. We propose structural reverse genetics, which combines structural characterization of proteins with mouse genetics, to identify new PP1-related therapeutic targets. The available mouse models confirm the pleiotropic action of PP1 in health and diseases. |
format | Online Article Text |
id | pubmed-7114192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71141922020-04-02 Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() Ferreira, Mónica Beullens, Monique Bollen, Mathieu Van Eynde, Aleyde Biochim Biophys Acta Mol Cell Res Article Protein phosphatase 1 (PP1) catalyzes more than half of all phosphoserine/threonine dephosphorylation reactions in mammalian cells. In vivo PP1 does not exist as a free catalytic subunit but is always associated with at least one regulatory PP1-interacting protein (PIP) to generate a large set of distinct holoenzymes. Each PP1 complex controls the dephosphorylation of only a small subset of PP1 substrates. We screened the literature for genetically engineered mouse models and identified models for all PP1 isoforms and 104 PIPs. PP1 itself and at least 49 PIPs were connected to human disease-associated phenotypes. Additionally, phenotypes related to 17 PIPs were clearly linked to altered PP1 function, while such information was lacking for 32 other PIPs. We propose structural reverse genetics, which combines structural characterization of proteins with mouse genetics, to identify new PP1-related therapeutic targets. The available mouse models confirm the pleiotropic action of PP1 in health and diseases. Elsevier B.V. 2019-01 2018-07-26 /pmc/articles/PMC7114192/ /pubmed/30056088 http://dx.doi.org/10.1016/j.bbamcr.2018.07.019 Text en © 2018 Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Ferreira, Mónica Beullens, Monique Bollen, Mathieu Van Eynde, Aleyde Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title | Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title_full | Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title_fullStr | Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title_full_unstemmed | Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title_short | Functions and therapeutic potential of protein phosphatase 1: Insights from mouse genetics() |
title_sort | functions and therapeutic potential of protein phosphatase 1: insights from mouse genetics() |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114192/ https://www.ncbi.nlm.nih.gov/pubmed/30056088 http://dx.doi.org/10.1016/j.bbamcr.2018.07.019 |
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