1. Lysine Methyltransferases Signaling: Histones are Just the Tip of the Iceberg
- Author
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Gaël S. Roth, Nicolas Reynoird, Florent Chuffart, Alexandre G. Casanova, Valentina Lukinović, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Reynoird, Nicolas
- Subjects
Cell signaling ,Jumonji Domain-Containing Histone Demethylases ,Methyltransferase ,Chromosomal Proteins, Non-Histone ,Biology ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,complex mixtures ,Biochemistry ,Methylation ,Histones ,03 medical and health sciences ,Methyllysine ,chemistry.chemical_compound ,0302 clinical medicine ,Neoplasms ,Lysine methylation ,Humans ,cancer ,Epigenetics ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Histone Demethylases ,0303 health sciences ,Lysine ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Cell Biology ,General Medicine ,Hypoxia-Inducible Factor 1, alpha Subunit ,KMT ,Chromatin ,Cell biology ,Gene Expression Regulation, Neoplastic ,Histone ,chemistry ,030220 oncology & carcinogenesis ,DNA methylation ,biology.protein ,bacteria ,protein lysine methyltransferases ,Protein Processing, Post-Translational ,Signal Transduction - Abstract
Protein lysine methylation is a functionally diverse post-translational modification involved in various major cellular processes. Lysine methylation can modulate proteins activity, stability, localization, and/or interaction, resulting in specific downstream signaling and biological outcomes. Lysine methylation is a dynamic and fine-tuned process, deregulation of which often leads to human pathologies. In particular, the lysine methylome and its associated signaling network can be linked to carcinogenesis and cancer progression. Histone modifications and chromatin regulation is a major aspect of lysine methylation importance, but increasing evidence suggests that a high relevance and impact of non-histone lysine methylation signaling has emerged in recent years. In this review, we draw an updated picture of the current scientific knowledge regarding non-histone lysine methylation signaling and its implication in physiological and pathological processes. We aim to demonstrate the significance of lysine methylation as a major and yet underestimated posttranslational modification, and to raise the importance of this modification in both epigenetic and cellular signaling by focusing on the observed activities of SET- and 7β-strandcontaining human lysine methyltransferases. Recent evidence suggests that what has been observed so far regarding lysine methylation’s implication in human pathologies is only the tip of the iceberg. Therefore, the exploration of the “methylome network” raises the possibility to use these enzymes and their substrates as promising new therapeutic targets for the development of future epigenetic and methyllysine signaling cancer treatments.
- Published
- 2020