Asymmetric dimethylation of ribosomal S6 kinase 2 regulates its cellular localisation and pro-survival function
Author(s)
Type
Journal Article
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.
Date Issued
2023-05
Date Acceptance
2023-05-05
Citation
International Journal of Molecular Sciences, 2023, 24 (10)
ISSN
1422-0067
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
24
Issue
10
Copyright Statement
© 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/).
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000997725100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
arginine methylation
ARGININE METHYLATION
AT-hook
BETA
BINDING
Biochemistry & Molecular Biology
Chemistry
Chemistry, Multidisciplinary
CHROMATIN
DNA
IN-VITRO
Life Sciences & Biomedicine
methyltransferases
PHOSPHORYLATION
Physical Sciences
PROTEIN
Science & Technology
SCLC
serine/threonine kinases
Publication Status
Published
Article Number
8806
Date Publish Online
2023-05-15