Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton
SETD2 is known to be the unique histone methyltransferase responsible for the trimethylation of the lysine 36 of histone H3 thus generating H3K36me3. This epigenetic mark is critical for transcriptional activation and elongation, DNA repair, mRNA splicing, and DNA methylation. Recurrent SETD2-inacti...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001313 |
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| author | Christina Michail Fernando Rodrigues Lima Mireille Viguier Frédérique Deshayes |
| author_facet | Christina Michail Fernando Rodrigues Lima Mireille Viguier Frédérique Deshayes |
| author_sort | Christina Michail |
| collection | DOAJ |
| description | SETD2 is known to be the unique histone methyltransferase responsible for the trimethylation of the lysine 36 of histone H3 thus generating H3K36me3. This epigenetic mark is critical for transcriptional activation and elongation, DNA repair, mRNA splicing, and DNA methylation. Recurrent SETD2-inactivating mutations and altered H3K36me3 levels are found in cancer at high frequency and numerous studies indicate that SETD2 acts as a tumor suppressor. Recently, SETD2 was further shown to methylate non-histone proteins particularly the cytoskeletal proteins tubulin and actin with subsequent impacts on cytoskeleton structure, mitosis and cell migration.Herein, we provide a review of the role of SETD2 in different cancers with special emphasis on the structural basis of the functions of this key lysine methyltransferase. Moreover, beyond the role of this enzyme in epigenetics and H3K36me3-dependent processes, we highlight the putative role of ''non-epigenetic/H3K36me3'' functions of SETD2 in cancer, particularly those involving the cytoskeleton. |
| format | Article |
| id | doaj-art-e28ad0a71a05407dad5e3418594feccd |
| institution | OA Journals |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-e28ad0a71a05407dad5e3418594feccd2025-08-20T01:57:59ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-01-015910109010.1016/j.neo.2024.101090Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeletonChristina Michail0Fernando Rodrigues Lima1Mireille Viguier2Frédérique Deshayes3Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, FranceUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, FranceCorresponding authors.; Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, FranceCorresponding authors.; Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, FranceSETD2 is known to be the unique histone methyltransferase responsible for the trimethylation of the lysine 36 of histone H3 thus generating H3K36me3. This epigenetic mark is critical for transcriptional activation and elongation, DNA repair, mRNA splicing, and DNA methylation. Recurrent SETD2-inactivating mutations and altered H3K36me3 levels are found in cancer at high frequency and numerous studies indicate that SETD2 acts as a tumor suppressor. Recently, SETD2 was further shown to methylate non-histone proteins particularly the cytoskeletal proteins tubulin and actin with subsequent impacts on cytoskeleton structure, mitosis and cell migration.Herein, we provide a review of the role of SETD2 in different cancers with special emphasis on the structural basis of the functions of this key lysine methyltransferase. Moreover, beyond the role of this enzyme in epigenetics and H3K36me3-dependent processes, we highlight the putative role of ''non-epigenetic/H3K36me3'' functions of SETD2 in cancer, particularly those involving the cytoskeleton.http://www.sciencedirect.com/science/article/pii/S1476558624001313CancerCytoskeletonGenetic alterationsHistonesSETD2Structure |
| spellingShingle | Christina Michail Fernando Rodrigues Lima Mireille Viguier Frédérique Deshayes Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton Neoplasia: An International Journal for Oncology Research Cancer Cytoskeleton Genetic alterations Histones SETD2 Structure |
| title | Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton |
| title_full | Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton |
| title_fullStr | Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton |
| title_full_unstemmed | Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton |
| title_short | Structure and function of the lysine methyltransferase SETD2 in cancer: From histones to cytoskeleton |
| title_sort | structure and function of the lysine methyltransferase setd2 in cancer from histones to cytoskeleton |
| topic | Cancer Cytoskeleton Genetic alterations Histones SETD2 Structure |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001313 |
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