Academic Journal
The role of serine/threonine phosphatases in human development: Evidence from congenital disorders
| Title: | The role of serine/threonine phosphatases in human development: Evidence from congenital disorders |
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| Authors: | Pieter Vaneynde, Iris Verbinnen, Veerle Janssens |
| Source: | Front Cell Dev Biol Frontiers in Cell and Developmental Biology, Vol 10 (2022) |
| Publisher Information: | Frontiers Media SA, 2022. |
| Publication Year: | 2022 |
| Subject Terms: | 0301 basic medicine, INTELLECTUAL DISABILITY, QH301-705.5, PYRUVATE-DEHYDROGENASE PHOSPHATASE, subaward A19-3376-S005, congenital disease, Cell and Developmental Biology, 03 medical and health sciences, WIP1 PHOSPHATASE, GLYCOGEN TARGETING SUBUNIT, CATALYTIC SUBUNIT, Biology (General), REGULATORY SUBUNIT, 0303 health sciences, Science & Technology, sex development disorder, 31 Biological sciences, neurodevelopmental disorders, PROTEIN PHOSPHATASE, Cell Biology, 32 Biomedical and clinical sciences, denovomutation, NOONAN SYNDROME, de novo mutation, 3. Good health, serine/threonine protein phosphatase, NOVO MISSENSE VARIANTS, SMALL-MOLECULE INHIBITORS, Life Sciences & Biomedicine, Developmental Biology |
| Description: | Reversible protein phosphorylation is a fundamental regulation mechanism in eukaryotic cell and organismal physiology, and in human health and disease. Until recently, and unlike protein kinases, mutations in serine/threonine protein phosphatases (PSP) had not been commonly associated with disorders of human development. Here, we have summarized the current knowledge on congenital diseases caused by mutations, inherited or de novo, in one of 38 human PSP genes, encoding a monomeric phosphatase or a catalytic subunit of a multimeric phosphatase. In addition, we highlight similar pathogenic mutations in genes encoding a specific regulatory subunit of a multimeric PSP. Overall, we describe 19 affected genes, and find that most pathogenic variants are loss-of-function, with just a few examples of gain-of-function alterations. Moreover, despite their widespread tissue expression, the large majority of congenital PSP disorders are characterised by brain-specific abnormalities, suggesting a generalized, major role for PSPs in brain development and function. However, even if the pathogenic mechanisms are relatively well understood for a small number of PSP disorders, this knowledge is still incomplete for most of them, and the further identification of downstream targets and effectors of the affected PSPs is eagerly awaited through studies in appropriate in vitro and in vivo disease models. Such lacking studies could elucidate the exact mechanisms through which these diseases act, and possibly open up new therapeutic avenues. |
| Document Type: | Article Other literature type |
| ISSN: | 2296-634X |
| DOI: | 10.3389/fcell.2022.1030119 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/36313552 https://doaj.org/article/652110a7a8294a96a5e2363b2d0a43ea |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....afff9be902af9f1e76995bcd20f78bd9 |
| Database: | OpenAIRE |
| ISSN: | 2296634X |
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| DOI: | 10.3389/fcell.2022.1030119 |