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Malki, I, Liepina, I, Kogelnik, N, Watmuff, H, Robinson, S, Lightfoot, A, Gonchar, O, Bottrill, A, Fry, AM and Dominguez, C (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. ISSN 0305-1048
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Cdk1 mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity and cellular functions.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
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: | Article |
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| Uncontrolled Keywords: | HCT116 Cells; Humans; CDC2 Protein Kinase; Adaptor Proteins, Signal Transducing; RNA-Binding Proteins; Cell Cycle Proteins; DNA-Binding Proteins; RNA; Alternative Splicing; Phosphorylation; HEK293 Cells; Humans; Adaptor Proteins, Signal Transducing; Alternative Splicing; CDC2 Protein Kinase; Cell Cycle Proteins; DNA-Binding Proteins; HEK293 Cells; Phosphorylation; RNA; RNA-Binding Proteins; HCT116 Cells; 05 Environmental Sciences; 06 Biological Sciences; 08 Information and Computing Sciences; Developmental Biology |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Oxford University Press |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 15 Jul 2024 13:17 |
| Last Modified: | 15 Jul 2024 13:30 |
| DOI or ID number: | 10.1093/nar/gkac1181 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/23748 |
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