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Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions
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Malki, Idir, Liepina, Inara, Kogelnik, Nora, Watmuff, Hollie, Robinson, Sue, Lightfoot, Adam, Gonchar, Oksana, Bottrill, Andrew, Fry, Andrew M. and Dominguez, Cyril (2022) Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions. Nucleic Acids Research, 50 (22). pp. 13045-13062. doi:10.1093/nar/gkac1181 ISSN 0305-1048.
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WRAP-Cdk1-mediated-threonine-phosphorylation-of-Sam68-modulates-its-RNA-binding-alternative-splicing-activity-and-cellular-functions-Bottrill-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2744Kb) | Preview |
Official URL: http://dx.doi.org/10.1093/nar/gkac1181
Abstract
Sam68, also known as KHDRBS1, is a member of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins and its role is modulated by post-translational modifications, including serine/threonine phosphorylation, that differ at various stages of the cell cycle. However, the molecular basis and mechanisms of these modulations remain largely unknown. Here, we combined mass spectrometry, nuclear magnetic resonance spectroscopy and cell biology techniques to provide a comprehensive post-translational modification mapping of Sam68 at different stages of the cell cycle in HEK293 and HCT116 cells. We established that Sam68 is specifically phosphorylated at T33 and T317 by Cdk1, and demonstrated that these phosphorylation events reduce the binding of Sam68 to RNA, control its cellular localization and reduce its alternative splicing activity, leading to a reduction in the induction of apoptosis and an increase in the proliferation of HCT116 cells.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | RNA, RNA-protein interactions, Protein binding, Phosphorylation , Cellular signal transduction | |||||||||||||||
| Journal or Publication Title: | Nucleic Acids Research | |||||||||||||||
| Publisher: | Oxford University Press | |||||||||||||||
| ISSN: | 0305-1048 | |||||||||||||||
| Official Date: | 20 December 2022 | |||||||||||||||
| Dates: |
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| Volume: | 50 | |||||||||||||||
| Number: | 22 | |||||||||||||||
| Page Range: | pp. 13045-13062 | |||||||||||||||
| DOI: | 10.1093/nar/gkac1181 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Date of first compliant deposit: | 23 January 2023 | |||||||||||||||
| Date of first compliant Open Access: | 25 January 2023 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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