Team
Protein methylation dynamics in cancer

Dpt: Signaling through Chromatin

Our research activities

Lysine methylation signaling is a dynamic and reversible process orchestrated by lysine methyltransferases (KMTs, which catalyze the addition of methyl groups), lysine demethylases (KDMs, which remove them), and dedicated methyl-binding proteins that translate these marks into relevant functional outcomes. While methylation of histones is well established as a fundamental regulator of chromatin structure and gene expression, it is increasingly clear that numerous non-histone proteins are also methylated. This suggests that lysine methylation may influence a wide range of cellular processes, and that its deregulation could contribute to various diseases. Despite its biological importance, relatively few non-histone lysine methylation substrates have been identified, and the functional consequences of this signaling remain poorly understood. Given its reversibility, specificity, and druggability, lysine methylation holds high therapeutic potential.

Our research aims to uncover previously uncharacterized KMTs and methylation signaling involved in tumorigenesis and to define novel targetable mechanisms in human cancers. Ultimately, our goal is to establish lysine methylation as a key regulator of cellular homeostasis and to provide new opportunities for therapeutic intervention in cancer.

View the team website reynoirdlab IAB_INFOGRAPHIES-Dynamique-methylation-proteine2.png

Nicolas REYNOIRD

Team leader

+33 (0)4 76 54 95 76

See file

Our research axes

The vast majority of lysine methyltransferases are still poorly characterized and for the most part their activity is unknown or not thoroughly analyzed. Several KMTs are overexpressed or altered in cancer and we aim to characterize key oncogenic lysine methylation signaling.

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Besides their functions in chromatin regulation, KMTs activities beyond histones modification have rarely been described. We aim to identify key non-histone methylation signaling involved in different biological processes regulating cell homeostasis.

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Lysine methylation is a finely regulated modification and a dynamic process thanks to demethylases. More than 30 demethylases have been identified in human, and very few have been characterized regarding potential activity on non-histone substrates. We aim to identify the related KDM counteracting key chromatin-independent cellular processes regulated by KMT.

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Our major publications

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Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis

A Casanova, G Roth, S Hausmann, X Lu, L Bischoff, E Froeliger, L Belmudes, E…

Cell Discovery 2024

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Methylation of ESCRT-III components regulates the timing of cytokinetic abscission

Richard A, Berthelet J, Judith D, Advedissian T, Espadas J, Jannot G, Amo A, Loew…

Nat Commun. 2024

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The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer

Sabeen Ikram, Apurv Rege, Maraki Y Negesse, Alexandre G Casanova, Nicolas Reynoird, Erin M Green

Science Advances 2023

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SMYD3 impedes small cell lung cancer sensitivity to alkylation damage through RNF113A methylation-phosphorylation crosstalk

Lukinović V, Hausmann S, Roth GS, Oyeniran C, Ahmad T, Tsao N, Brickner JR, Casanova…

Cancer Discovery 2022 Sep 2;12(9):2158-2179. doi: 10.1158/2159-8290.CD-21-0205. PMID: 35819319

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Aberrant RNA methylation triggers recruitment of an alkylation repair complex

Tsao N, Brickner JR, Rodell R, Ganguly A, Wood M, Oyeniran C, Ahmad T, Sun…

Molecular Cell. 2021 Oct 21;81(20):4228-4242.e8. doi: 10.1016/j.molcel.2021.09.024. PMID: 34686315

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Lysine Methyltransferases Signaling: Histones are Just the Tip of the Iceberg

Lukinović V, Casanova AG, Roth GS, Chuffart F, Reynoird N.

Curr Protein Pept Sci 2020 21(7):655-674. doi: 10.2174/1871527319666200102101608. PMID: 31894745

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Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer

Reynoird N, Mazur PK, Stellfeld T, Flores NM, Lofgren SM, Carlson SM, Brambilla E, Hainaut…

Genes Dev 2016 Apr 1;30(7):772-85. doi: 10.1101/gad.275529.115. Epub 2016 Mar 17. PMID: 26988419

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SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer

Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, Van…

Nature 2014 Jun 12;510(7504):283-7. doi: 10.1038/nature13320. Epub 2014 May 21. PMID: 24847881

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Our activities in pictures

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Our collaborations

  • Mazur lab, MD Anderson Cancer Center, University of Texas, USA
  • EDyP Lab, IRIG, France
  • Many others !

Our technologies

  • High-throughput proteomics
  • Cell engineering
  • In vitro radiolabeled methylation assay
  • Biochemistry and molecular biology tools
  • Many more!