An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes
Haithem Barbour,
Nadine Sen Nkwe,
Benjamin Estavoyer,
Clémence Messmer,
Mila Gushul-Leclaire,
Romain Villot,
Maxime Uriarte,
Karine Boulay,
Sari Hlayhel,
Bassel Farhat,
Eric Milot,
Frédérick A. Mallette,
Salima Daou,
El Bachir Affar
Affiliations
Haithem Barbour
Biomedical Sciences Programs, University of Montreal, Montreal, QC H3C 3T5, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Nadine Sen Nkwe
Molecular Biology Programs, University of Montreal, Montreal, QC H3A 0G4, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Benjamin Estavoyer
Molecular Biology Programs, University of Montreal, Montreal, QC H3A 0G4, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Clémence Messmer
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Mila Gushul-Leclaire
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Romain Villot
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Maxime Uriarte
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Karine Boulay
Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Sari Hlayhel
Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Bassel Farhat
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada
Eric Milot
Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada; Department of Medicine, University of Montréal, Montreal, QC H3C 3J7, Canada; Corresponding author
Frédérick A. Mallette
Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada; Department of Medicine, University of Montréal, Montreal, QC H3C 3J7, Canada; Corresponding author
Salima Daou
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Corresponding author
El Bachir Affar
Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada; Department of Medicine, University of Montréal, Montreal, QC H3C 3J7, Canada; Corresponding author
Summary: Ubiquitination is an important post-translational modification (PTM) that regulates a large spectrum of cellular processes in eukaryotes. Abnormalities in ubiquitin signaling underlie numerous human pathologies including cancer and neurodegeneration. Much progress has been made during the last three decades in understanding how ubiquitin ligases recognize their substrates and how ubiquitination is orchestrated. Several mechanisms of regulation have evolved to prevent promiscuity including the assembly of ubiquitin ligases in multi-protein complexes with dedicated subunits and specific post-translational modifications of these enzymes and their co-factors. Here, we outline another layer of complexity involving the coordinated access of E3 ligases to substrates. We provide an extensive inventory of ubiquitination crosstalk with multiple PTMs including SUMOylation, phosphorylation, methylation, acetylation, hydroxylation, prolyl isomerization, PARylation, and O-GlcNAcylation. We discuss molecular mechanisms by which PTMs orchestrate ubiquitination, thus increasing its specificity as well as its crosstalk with other signaling pathways to ensure cell homeostasis.
