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Unmasking the mammalian SET domain-containing protein 4
SET domain-containing protein 4 (SETD4) is a member of a unique class of protein lysine methyltransferases. Here, we introduce the basic features of SETD4 and summarize the key findings from recent studies with emphases on its roles in tissue development and tumorigenesis, and its methylation substr...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277757/ https://www.ncbi.nlm.nih.gov/pubmed/35854936 http://dx.doi.org/10.1093/narcan/zcac021 |
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author | Wang, Yuan Shen, Zhiyuan |
author_facet | Wang, Yuan Shen, Zhiyuan |
author_sort | Wang, Yuan |
collection | PubMed |
description | SET domain-containing protein 4 (SETD4) is a member of a unique class of protein lysine methyltransferases. Here, we introduce the basic features of SETD4 and summarize the key findings from recent studies with emphases on its roles in tissue development and tumorigenesis, and its methylation substrates. SETD4 is expressed in stem/progenitor cells. Ablation of Setd4(+) cells impedes the repopulation of acinar cells after pancreatic injury. Setd4 deletion in mice promotes the recovery of radiation-induced bone marrow (BM) failure by boosting the function of BM niche, facilitates the generation of endothelial cells and neovascularization of capillary vessels in the heart, enhances the proliferation of BM mesenchymal stem cells and disrupts the TLR4 signaling in BM-derived macrophages. SETD4 expression is also associated with the maintenance of quiescent breast cancer stem cells. While mouse Setd4 knockout delays radiation-induced T-lymphoma formation, elevated SETD4 expression has been observed in some proliferative cancer cells and is associated with a pro-survival potential. Oncogenic fusions of SETD4 have also been identified in cancer, albeit rare. In addition, SETD4 methylates lysine-570 in the C-terminal globular domain of KU70, which enables KU70 translocation to cytoplasm to suppress apoptosis. |
format | Online Article Text |
id | pubmed-9277757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92777572022-07-18 Unmasking the mammalian SET domain-containing protein 4 Wang, Yuan Shen, Zhiyuan NAR Cancer Short Review SET domain-containing protein 4 (SETD4) is a member of a unique class of protein lysine methyltransferases. Here, we introduce the basic features of SETD4 and summarize the key findings from recent studies with emphases on its roles in tissue development and tumorigenesis, and its methylation substrates. SETD4 is expressed in stem/progenitor cells. Ablation of Setd4(+) cells impedes the repopulation of acinar cells after pancreatic injury. Setd4 deletion in mice promotes the recovery of radiation-induced bone marrow (BM) failure by boosting the function of BM niche, facilitates the generation of endothelial cells and neovascularization of capillary vessels in the heart, enhances the proliferation of BM mesenchymal stem cells and disrupts the TLR4 signaling in BM-derived macrophages. SETD4 expression is also associated with the maintenance of quiescent breast cancer stem cells. While mouse Setd4 knockout delays radiation-induced T-lymphoma formation, elevated SETD4 expression has been observed in some proliferative cancer cells and is associated with a pro-survival potential. Oncogenic fusions of SETD4 have also been identified in cancer, albeit rare. In addition, SETD4 methylates lysine-570 in the C-terminal globular domain of KU70, which enables KU70 translocation to cytoplasm to suppress apoptosis. Oxford University Press 2022-07-13 /pmc/articles/PMC9277757/ /pubmed/35854936 http://dx.doi.org/10.1093/narcan/zcac021 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Review Wang, Yuan Shen, Zhiyuan Unmasking the mammalian SET domain-containing protein 4 |
title | Unmasking the mammalian SET domain-containing protein 4 |
title_full | Unmasking the mammalian SET domain-containing protein 4 |
title_fullStr | Unmasking the mammalian SET domain-containing protein 4 |
title_full_unstemmed | Unmasking the mammalian SET domain-containing protein 4 |
title_short | Unmasking the mammalian SET domain-containing protein 4 |
title_sort | unmasking the mammalian set domain-containing protein 4 |
topic | Short Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277757/ https://www.ncbi.nlm.nih.gov/pubmed/35854936 http://dx.doi.org/10.1093/narcan/zcac021 |
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