Insights in Post-Translational Modifications: Ubiquitin and SUMO

Abstract

Both ubiquitination and SUMOylation are dynamic post-translational modifications that regulate thousands of target proteins to control virtually every cellular process. Unfortunately, the detailed mechanisms of how all these cellular processes are regulated by both modifications remain unclear. Target proteins can be modified by one or several moieties, giving rise to polymers of different morphology. The conjugation cascades of both modifications comprise a few activating and conjugating enzymes but close to thousands of ligating enzymes (E3s) in the case of ubiquitination. As a result, these E3s give substrate specificity and can form polymers on a target protein. Polymers can be quickly modified forming branches or cleaving chains leading the target protein to its cellular fate. The recent development of mass spectrometry(MS) -based approaches has increased the understanding of ubiquitination and SUMOylation by finding essential modified targets in particular signaling pathways. Here, we perform a concise overview comprising from the basic mechanisms of both ubiquitination and SUMOylation to recent MS-based approaches aimed to find specific targets for particular E3 enzymes.

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

“…Histone ubiquitylation is a post-translational modification, characterized by the attaching of a small regulatory protein ubiquitin to the histone proteins. The name of a protein refers its ubiquity in all eukaryotic organisms [ 220 ].…”

“…Ubiquitin contains seven acceptor lysines (K6, K11, K27, K29, K33, K48 and K63), which are mostly located on histones H2A and H2B [ 220 ]. In mammalian systems, both H2A and H2B are ubiquitylated at K119 and K120, respectively [ 221 ].…”

“…Depending on the lysine and the configuration of the linkages, the ubiquitylation can drive different cellular outcomes. The addition of a ubiquitin molecule to histone results in monoubiquitination if conjugation appears at one of the lysines and multi-monoubiquitination when several lysines are ubiquitinylated [ 220 ]. Histone monoubiquitylation has a special role in DNA damage repair [ 223 ] and is associated with tumors and neurodevelopmental disorders; multi-monoubiquitylation has been mainly reported in endocytosis [ 220 ].…”

“…The addition of a ubiquitin molecule to histone results in monoubiquitination if conjugation appears at one of the lysines and multi-monoubiquitination when several lysines are ubiquitinylated [ 220 ]. Histone monoubiquitylation has a special role in DNA damage repair [ 223 ] and is associated with tumors and neurodevelopmental disorders; multi-monoubiquitylation has been mainly reported in endocytosis [ 220 ]. The ubiquitin can also form polymers and therefore provide the poly-ubiquitylation of proteins [ 224 ].…”

“…The conjugation of any SUMO member to a substrate is termed sumoylation. Similarly to ubiquitination, sumoylation is processed in a three-step enzymatic cascade that involves a dimeric E1 activating enzyme (SAE1 and SAE2), an E2 conjugating enzyme (Ubc9) and several SUMO E3 enzymes [ 220 ]. The sumoylation of histones is a highly dynamic process.…”