Khalil, M.I. orcid.org/0000-0001-7629-4357, Ismail, H.M. orcid.org/0000-0003-2049-1065, Panasyuk, G. orcid.org/0000-0002-5591-848X et al. (4 more authors) (2023) Asymmetric dimethylation of ribosomal S6 kinase 2 regulates its cellular localisation and pro-survival function. International Journal of Molecular Sciences, 24 (10). 8806. ISSN 1661-6596
Abstract
Ribosomal S6 kinases (S6Ks) are critical regulators of cell growth, homeostasis, and survival, with dysregulation of these kinases found to be associated with various malignancies. While S6K1 has been extensively studied, S6K2 has been neglected despite its clear involvement in cancer progression. Protein arginine methylation is a widespread post-translational modification regulating many biological processes in mammalian cells. Here, we report that p54-S6K2 is asymmetrically dimethylated at Arg-475 and Arg-477, two residues conserved amongst mammalian S6K2s and several AT-hook-containing proteins. We demonstrate that this methylation event results from the association of S6K2 with the methyltransferases PRMT1, PRMT3, and PRMT6 in vitro and in vivo and leads to nuclear the localisation of S6K2 that is essential to the pro-survival effects of this kinase to starvation-induced cell death. Taken together, our findings highlight a novel post-translational modification regulating the function of p54-S6K2 that may be particularly relevant to cancer progression where general Arg-methylation is often elevated.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | AT-hook; SCLC; arginine methylation; methyltransferases; serine/threonine kinases; Animals; Phosphorylation; Ribosomal Protein S6 Kinases, 90-kDa; Ribosomal Protein S6 Kinases; Biological Phenomena; Ribosomal Protein S6 Kinases, 70-kDa; Mammals |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Jun 2023 10:58 |
Last Modified: | 12 Jun 2023 10:58 |
Published Version: | http://dx.doi.org/10.3390/ijms24108806 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/ijms24108806 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:200343 |