Death-associated protein kinase 1: a double-edged sword in health and disease
Death-associated protein kinase 1 (DAPK1) is a Ca2+/calmodulin-regulated serine/threonine kinase that orchestrates a wide array of cellular activities. It is intricately regulated through multiple mechanisms, including intramolecular signaling and interactions with other proteins, such as kinases an...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593394/full |
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| author | Xiuli Zhang Yehuda G. Assaraf Yao Lin |
| author_facet | Xiuli Zhang Yehuda G. Assaraf Yao Lin |
| author_sort | Xiuli Zhang |
| collection | DOAJ |
| description | Death-associated protein kinase 1 (DAPK1) is a Ca2+/calmodulin-regulated serine/threonine kinase that orchestrates a wide array of cellular activities. It is intricately regulated through multiple mechanisms, including intramolecular signaling and interactions with other proteins, such as kinases and phosphatases. DAPK1 plays a pivotal role in regulating various biological processes, including apoptosis and autophagy, and is implicated in pathogenesis of several disorders, such as cancer, stroke and brain damage, neurodegenerative and within their kinase domains. In 2014, a collection of reviews was cardiovascular diseases, wound healing, kidney injury, and tuberous sclerosis complex. In light of its biological significance, several small molecule modulators of DAPK1 have been developed for therapeutic purposes and as probe compounds to enhance the mechanistic understanding of DAPK1-mediated biological functions. However, the repertoire of available small molecules remains limited, underscoring the need for further research to discover novel strategies for the activation or inhibition of DAPK1. From this perspective, we primarily discuss the structure, biological function, and role of DAPK1 in health and disease, as well as the recently identified small molecule inhibitors and activators. This analysis offers valuable insights for advancing research in the DAPK1 field. |
| format | Article |
| id | doaj-art-99995cc8f829489cb05d5f77b6bef44e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-99995cc8f829489cb05d5f77b6bef44e2025-08-21T04:10:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.15933941593394Death-associated protein kinase 1: a double-edged sword in health and diseaseXiuli Zhang0Yehuda G. Assaraf1Yao Lin2The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, College of Integrative Medicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaThe Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, College of Integrative Medicine, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaDeath-associated protein kinase 1 (DAPK1) is a Ca2+/calmodulin-regulated serine/threonine kinase that orchestrates a wide array of cellular activities. It is intricately regulated through multiple mechanisms, including intramolecular signaling and interactions with other proteins, such as kinases and phosphatases. DAPK1 plays a pivotal role in regulating various biological processes, including apoptosis and autophagy, and is implicated in pathogenesis of several disorders, such as cancer, stroke and brain damage, neurodegenerative and within their kinase domains. In 2014, a collection of reviews was cardiovascular diseases, wound healing, kidney injury, and tuberous sclerosis complex. In light of its biological significance, several small molecule modulators of DAPK1 have been developed for therapeutic purposes and as probe compounds to enhance the mechanistic understanding of DAPK1-mediated biological functions. However, the repertoire of available small molecules remains limited, underscoring the need for further research to discover novel strategies for the activation or inhibition of DAPK1. From this perspective, we primarily discuss the structure, biological function, and role of DAPK1 in health and disease, as well as the recently identified small molecule inhibitors and activators. This analysis offers valuable insights for advancing research in the DAPK1 field.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593394/fullDAPK1biological processessmall moleculeguardians of inflammationhealth |
| spellingShingle | Xiuli Zhang Yehuda G. Assaraf Yao Lin Death-associated protein kinase 1: a double-edged sword in health and disease Frontiers in Immunology DAPK1 biological processes small molecule guardians of inflammation health |
| title | Death-associated protein kinase 1: a double-edged sword in health and disease |
| title_full | Death-associated protein kinase 1: a double-edged sword in health and disease |
| title_fullStr | Death-associated protein kinase 1: a double-edged sword in health and disease |
| title_full_unstemmed | Death-associated protein kinase 1: a double-edged sword in health and disease |
| title_short | Death-associated protein kinase 1: a double-edged sword in health and disease |
| title_sort | death associated protein kinase 1 a double edged sword in health and disease |
| topic | DAPK1 biological processes small molecule guardians of inflammation health |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1593394/full |
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