NSD family proteins: Rising stars as therapeutic targets
Epigenetic modifications, including DNA methylation and histone post-translational modifications, intricately regulate gene expression patterns by influencing DNA accessibility and chromatin structure in higher organisms. These modifications are heritable, are independent of primary DNA sequences, u...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892724000063 |
| _version_ | 1827301501764108288 |
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| author | Lin He Yiping Cao Luyang Sun |
| author_facet | Lin He Yiping Cao Luyang Sun |
| author_sort | Lin He |
| collection | DOAJ |
| description | Epigenetic modifications, including DNA methylation and histone post-translational modifications, intricately regulate gene expression patterns by influencing DNA accessibility and chromatin structure in higher organisms. These modifications are heritable, are independent of primary DNA sequences, undergo dynamic changes during development and differentiation, and are frequently disrupted in human diseases. The reversibility of epigenetic modifications makes them promising targets for therapeutic intervention and drugs targeting epigenetic regulators (e.g., tazemetostat, targeting the H3K27 methyltransferase EZH2) have been applied in clinical therapy for multiple cancers. The NSD family of H3K36 methyltransferase enzymes—including NSD1 (KMT3B), NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1)—are now receiving drug development attention, with the exciting advent of an NSD2 inhibitor (KTX-1001) advancing to Phase I clinical trials for relapsed or refractory multiple myeloma. NSD proteins recognize and catalyze methylation of histone lysine marks, thereby regulating chromatin integrity and gene expression. Multiple studies have implicated NSD proteins in human disease, noting impacts from translocations, aberrant expression, and various dysfunctional somatic mutations. Here, we review the biological functions of NSD proteins, epigenetic cooperation related to NSD proteins, and the accumulating evidence linking these proteins to developmental disorders and tumorigenesis, while additionally considering prospects for the development of innovative epigenetic therapies. |
| first_indexed | 2024-03-08T03:29:04Z |
| format | Article |
| id | doaj.art-22d074ddc9164b66afb301575015ea3e |
| institution | Directory Open Access Journal |
| issn | 2772-8927 |
| language | English |
| last_indexed | 2024-04-24T16:24:20Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj.art-22d074ddc9164b66afb301575015ea3e2024-03-31T04:38:14ZengElsevierCell Insight2772-89272024-04-0132100151NSD family proteins: Rising stars as therapeutic targetsLin He0Yiping Cao1Luyang Sun2Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, China; Corresponding author. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing 100191, China.Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, China; Corresponding author. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing 100191, China.Epigenetic modifications, including DNA methylation and histone post-translational modifications, intricately regulate gene expression patterns by influencing DNA accessibility and chromatin structure in higher organisms. These modifications are heritable, are independent of primary DNA sequences, undergo dynamic changes during development and differentiation, and are frequently disrupted in human diseases. The reversibility of epigenetic modifications makes them promising targets for therapeutic intervention and drugs targeting epigenetic regulators (e.g., tazemetostat, targeting the H3K27 methyltransferase EZH2) have been applied in clinical therapy for multiple cancers. The NSD family of H3K36 methyltransferase enzymes—including NSD1 (KMT3B), NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1)—are now receiving drug development attention, with the exciting advent of an NSD2 inhibitor (KTX-1001) advancing to Phase I clinical trials for relapsed or refractory multiple myeloma. NSD proteins recognize and catalyze methylation of histone lysine marks, thereby regulating chromatin integrity and gene expression. Multiple studies have implicated NSD proteins in human disease, noting impacts from translocations, aberrant expression, and various dysfunctional somatic mutations. Here, we review the biological functions of NSD proteins, epigenetic cooperation related to NSD proteins, and the accumulating evidence linking these proteins to developmental disorders and tumorigenesis, while additionally considering prospects for the development of innovative epigenetic therapies.http://www.sciencedirect.com/science/article/pii/S2772892724000063Epigenetic modificationCell identityHistone methyltransferaseEpigenetic inhibitorHistone codeNSD |
| spellingShingle | Lin He Yiping Cao Luyang Sun NSD family proteins: Rising stars as therapeutic targets Cell Insight Epigenetic modification Cell identity Histone methyltransferase Epigenetic inhibitor Histone code NSD |
| title | NSD family proteins: Rising stars as therapeutic targets |
| title_full | NSD family proteins: Rising stars as therapeutic targets |
| title_fullStr | NSD family proteins: Rising stars as therapeutic targets |
| title_full_unstemmed | NSD family proteins: Rising stars as therapeutic targets |
| title_short | NSD family proteins: Rising stars as therapeutic targets |
| title_sort | nsd family proteins rising stars as therapeutic targets |
| topic | Epigenetic modification Cell identity Histone methyltransferase Epigenetic inhibitor Histone code NSD |
| url | http://www.sciencedirect.com/science/article/pii/S2772892724000063 |
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