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

doi:10.1016/j.isci.2023.106276

An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes

iScience. 2023 Feb 26;26(5):106276. doi: 10.1016/j.isci.2023.106276. eCollection 2023 May 19.

Authors

Haithem Barbour^{1

2}, Nadine Sen Nkwe^{3

2}, Benjamin Estavoyer^{3

2}, Clémence Messmer^{4

2}, Mila Gushul-Leclaire^{4

2}, Romain Villot^{4

2}, Maxime Uriarte^{4

2}, Karine Boulay², Sari Hlayhel², Bassel Farhat^{4

2}, Eric Milot^{2

5}, Frédérick A Mallette^{4

2

5}, Salima Daou⁶, El Bachir Affar^{2

5}

Affiliations

¹ Biomedical Sciences Programs, University of Montreal, Montreal, QC H3C 3T5, Canada.
² Maisonneuve-Rosemont Hospital Research Center, Montréal, QC H1T 2M4, Canada.
³ Molecular Biology Programs, University of Montreal, Montreal, QC H3A 0G4, Canada.
⁴ Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada.
⁵ Department of Medicine, University of Montréal, Montreal, QC H3C 3J7, Canada.
⁶ Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Abstract

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.

Keywords: Biochemistry; Biological sciences; Cell biology; Molecular biology.

Publication types

Review