Post-translational modifications of CDK5 and their biological roles in cancer
Abstract Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2021-07-01
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| Series: | Molecular Biomedicine |
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| Online Access: | https://doi.org/10.1186/s43556-021-00029-0 |
| _version_ | 1819141933022314496 |
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| author | Gui-Bin Gao Yue Sun Run-Dong Fang Ying Wang Yang Wang Qing-Yu He |
| author_facet | Gui-Bin Gao Yue Sun Run-Dong Fang Ying Wang Yang Wang Qing-Yu He |
| author_sort | Gui-Bin Gao |
| collection | DOAJ |
| description | Abstract Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted. |
| first_indexed | 2024-12-22T12:02:19Z |
| format | Article |
| id | doaj.art-4f6dcb8b0d6c43f1853fbc241ac930b7 |
| institution | Directory Open Access Journal |
| issn | 2662-8651 |
| language | English |
| last_indexed | 2024-12-22T12:02:19Z |
| publishDate | 2021-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Molecular Biomedicine |
| spelling | doaj.art-4f6dcb8b0d6c43f1853fbc241ac930b72022-12-21T18:26:33ZengSpringerMolecular Biomedicine2662-86512021-07-012111510.1186/s43556-021-00029-0Post-translational modifications of CDK5 and their biological roles in cancerGui-Bin Gao0Yue Sun1Run-Dong Fang2Ying Wang3Yang Wang4Qing-Yu He5MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan UniversityMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan UniversityMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan UniversityInstitute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da UniversidadeMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan UniversityMOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan UniversityAbstract Post-translational modifications (PTMs) of Cyclin-dependent kinase 5 (CDK5) have emerged as important regulatory mechanisms that modulate cancer development in patients. Though CDK5 is an atypical member of the cyclin-dependent kinase family, its aberrant expression links to cell proliferation, DNA damage response, apoptosis, migration and angiogenesis in cancer. Current studies suggested that, new PTMs on CDK5, including S-nitrosylation, sumoylation, and acetylation, serve as molecular switches to control the kinase activity of CDK5 in the cell. However, a majority of these modifications and their biological significance in cancer remain uncharacterized. In this review, we discussed the role of PTMs on CDK5-mediated signaling cascade, and their possible mechanisms of action in malignant tumors, as well as the challenges and future perspectives in this field. On the basis of the newly identified regulatory signaling pathways of CDK5 related to PTMs, researchers have investigated the cancer therapeutic potential of chemical compounds, small-molecule inhibitors, and competitive peptides by targeting CDK5 and its PTMs. Results of these preclinical studies demonstrated that targeting PTMs of CDK5 yields promising antitumor effects and that clinical translation of these therapeutic strategies is warranted.https://doi.org/10.1186/s43556-021-00029-0CDK5Posttranslational modificationsCancer |
| spellingShingle | Gui-Bin Gao Yue Sun Run-Dong Fang Ying Wang Yang Wang Qing-Yu He Post-translational modifications of CDK5 and their biological roles in cancer Molecular Biomedicine CDK5 Posttranslational modifications Cancer |
| title | Post-translational modifications of CDK5 and their biological roles in cancer |
| title_full | Post-translational modifications of CDK5 and their biological roles in cancer |
| title_fullStr | Post-translational modifications of CDK5 and their biological roles in cancer |
| title_full_unstemmed | Post-translational modifications of CDK5 and their biological roles in cancer |
| title_short | Post-translational modifications of CDK5 and their biological roles in cancer |
| title_sort | post translational modifications of cdk5 and their biological roles in cancer |
| topic | CDK5 Posttranslational modifications Cancer |
| url | https://doi.org/10.1186/s43556-021-00029-0 |
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