Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies
Arginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/21/5443 |
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| author | Camille Sauter John Simonet Fabien Guidez Baptiste Dumétier Baptiste Pernon Mary Callanan Jean-Noël Bastie Romain Aucagne Laurent Delva |
| author_facet | Camille Sauter John Simonet Fabien Guidez Baptiste Dumétier Baptiste Pernon Mary Callanan Jean-Noël Bastie Romain Aucagne Laurent Delva |
| author_sort | Camille Sauter |
| collection | DOAJ |
| description | Arginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they form on a molecule of arginine. During the formation and maturation of the different types of blood cells, PRMTs play a central role by controlling cell differentiation at the transcriptional level. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails’ arginine. Chemical tools have been developed to inhibit the activity of PRMTs and have been tested in several models of hematological malignancies, including primary samples from patients, xenografts into immunodeficient mice, mouse models, and human cell lines. They show a significant effect by reducing cell viability and increasing the overall survival of mice. PRMT5 inhibitors have a strong therapeutic potential, as phase I clinical trials in hematological malignancies that use these molecules show promising results, thus, underlining PRMT inhibitors as useful therapeutic tools for cancer treatment in the future. |
| first_indexed | 2024-03-09T19:12:22Z |
| format | Article |
| id | doaj.art-8b2e6c5019ab4fdba06b802c4f06c938 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:12:22Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8b2e6c5019ab4fdba06b802c4f06c9382023-11-24T04:04:30ZengMDPI AGCancers2072-66942022-11-011421544310.3390/cancers14215443Protein Arginine Methyltransferases as Therapeutic Targets in Hematological MalignanciesCamille Sauter0John Simonet1Fabien Guidez2Baptiste Dumétier3Baptiste Pernon4Mary Callanan5Jean-Noël Bastie6Romain Aucagne7Laurent Delva8Inserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInserm U1231, Team Epi2THM, LipSTIC Labex, UFR des Sciences de Santé, Université de Bourgogne, Université Bourgogne Franche-Comté, 21000 Dijon, FranceArginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they form on a molecule of arginine. During the formation and maturation of the different types of blood cells, PRMTs play a central role by controlling cell differentiation at the transcriptional level. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails’ arginine. Chemical tools have been developed to inhibit the activity of PRMTs and have been tested in several models of hematological malignancies, including primary samples from patients, xenografts into immunodeficient mice, mouse models, and human cell lines. They show a significant effect by reducing cell viability and increasing the overall survival of mice. PRMT5 inhibitors have a strong therapeutic potential, as phase I clinical trials in hematological malignancies that use these molecules show promising results, thus, underlining PRMT inhibitors as useful therapeutic tools for cancer treatment in the future.https://www.mdpi.com/2072-6694/14/21/5443hematological malignanciesarginine methylationPRMTinhibitorsclinical trials |
| spellingShingle | Camille Sauter John Simonet Fabien Guidez Baptiste Dumétier Baptiste Pernon Mary Callanan Jean-Noël Bastie Romain Aucagne Laurent Delva Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies Cancers hematological malignancies arginine methylation PRMT inhibitors clinical trials |
| title | Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies |
| title_full | Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies |
| title_fullStr | Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies |
| title_full_unstemmed | Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies |
| title_short | Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies |
| title_sort | protein arginine methyltransferases as therapeutic targets in hematological malignancies |
| topic | hematological malignancies arginine methylation PRMT inhibitors clinical trials |
| url | https://www.mdpi.com/2072-6694/14/21/5443 |
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