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RUNX2-modifying enzymes: therapeutic targets for bone diseases

RUNX2 is a master transcription factor of osteoblast differentiation. RUNX2 expression in the bone and osteogenic front of a suture is crucial for cranial suture closure and membranous bone morphogenesis. In this manner, the regulation of RUNX2 is precisely controlled by multiple posttranslational m...

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Autores principales: Kim, Woo-Jin, Shin, Hye-Lim, Kim, Bong-Soo, Kim, Hyun-Jung, Ryoo, Hyun-Mo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080656/
https://www.ncbi.nlm.nih.gov/pubmed/32788656
http://dx.doi.org/10.1038/s12276-020-0471-4
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author Kim, Woo-Jin
Shin, Hye-Lim
Kim, Bong-Soo
Kim, Hyun-Jung
Ryoo, Hyun-Mo
author_facet Kim, Woo-Jin
Shin, Hye-Lim
Kim, Bong-Soo
Kim, Hyun-Jung
Ryoo, Hyun-Mo
author_sort Kim, Woo-Jin
collection PubMed
description RUNX2 is a master transcription factor of osteoblast differentiation. RUNX2 expression in the bone and osteogenic front of a suture is crucial for cranial suture closure and membranous bone morphogenesis. In this manner, the regulation of RUNX2 is precisely controlled by multiple posttranslational modifications (PTMs) mediated by the stepwise recruitment of multiple enzymes. Genetic defects in RUNX2 itself or in its PTM regulatory pathways result in craniofacial malformations. Haploinsufficiency in RUNX2 causes cleidocranial dysplasia (CCD), which is characterized by open fontanelle and hypoplastic clavicles. In contrast, gain-of-function mutations in FGFRs, which are known upstream stimulating signals of RUNX2 activity, cause craniosynostosis (CS) characterized by premature suture obliteration. The identification of these PTM cascades could suggest suitable drug targets for RUNX2 regulation. In this review, we will focus on the mechanism of RUNX2 regulation mediated by PTMs, such as phosphorylation, prolyl isomerization, acetylation, and ubiquitination, and we will summarize the therapeutics associated with each PTM enzyme for the treatment of congenital cranial suture anomalies.
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spelling pubmed-80806562021-04-29 RUNX2-modifying enzymes: therapeutic targets for bone diseases Kim, Woo-Jin Shin, Hye-Lim Kim, Bong-Soo Kim, Hyun-Jung Ryoo, Hyun-Mo Exp Mol Med Review Article RUNX2 is a master transcription factor of osteoblast differentiation. RUNX2 expression in the bone and osteogenic front of a suture is crucial for cranial suture closure and membranous bone morphogenesis. In this manner, the regulation of RUNX2 is precisely controlled by multiple posttranslational modifications (PTMs) mediated by the stepwise recruitment of multiple enzymes. Genetic defects in RUNX2 itself or in its PTM regulatory pathways result in craniofacial malformations. Haploinsufficiency in RUNX2 causes cleidocranial dysplasia (CCD), which is characterized by open fontanelle and hypoplastic clavicles. In contrast, gain-of-function mutations in FGFRs, which are known upstream stimulating signals of RUNX2 activity, cause craniosynostosis (CS) characterized by premature suture obliteration. The identification of these PTM cascades could suggest suitable drug targets for RUNX2 regulation. In this review, we will focus on the mechanism of RUNX2 regulation mediated by PTMs, such as phosphorylation, prolyl isomerization, acetylation, and ubiquitination, and we will summarize the therapeutics associated with each PTM enzyme for the treatment of congenital cranial suture anomalies. Nature Publishing Group UK 2020-08-13 /pmc/articles/PMC8080656/ /pubmed/32788656 http://dx.doi.org/10.1038/s12276-020-0471-4 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Kim, Woo-Jin
Shin, Hye-Lim
Kim, Bong-Soo
Kim, Hyun-Jung
Ryoo, Hyun-Mo
RUNX2-modifying enzymes: therapeutic targets for bone diseases
title RUNX2-modifying enzymes: therapeutic targets for bone diseases
title_full RUNX2-modifying enzymes: therapeutic targets for bone diseases
title_fullStr RUNX2-modifying enzymes: therapeutic targets for bone diseases
title_full_unstemmed RUNX2-modifying enzymes: therapeutic targets for bone diseases
title_short RUNX2-modifying enzymes: therapeutic targets for bone diseases
title_sort runx2-modifying enzymes: therapeutic targets for bone diseases
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080656/
https://www.ncbi.nlm.nih.gov/pubmed/32788656
http://dx.doi.org/10.1038/s12276-020-0471-4
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