The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System

Abstract

Owing to a sessile lifestyle in nature, plants are routinely faced with diverse hostile environments such as various abiotic and biotic stresses, which lead to accumulation of free radicals in cells, cell damage, protein denaturation, etc., causing adverse effects to cells. During the evolution process, plants formed defense systems composed of numerous complex gene regulatory networks and signal transduction pathways to regulate and maintain the cell homeostasis. Among them, ubiquitin-proteasome pathway (UPP) is the most versatile cellular signal system as well as a powerful mechanism for regulating many aspects of the cell physiology because it removes most of the abnormal and short-lived peptides and proteins. In this system, the ubiquitin-conjugating enzyme (E2) plays a critical role in transporting ubiquitin from the ubiquitin-activating enzyme (E1) to the ubiquitin-ligase enzyme (E3) and substrate. Nevertheless, the comprehensive study regarding the role of E2 enzymes in plants remains unexplored. In this review, the ubiquitination process and the regulatory role that E2 enzymes play in plants are primarily discussed, with the focus particularly put on E2 s regulation of biological functions of the cell. especially E3s (more than 1400 potential E3s are encoded in A. thaliana genome) and E2s (37 E2s are encoded in A. thaliana genome) [8,21]. Therefore, it will be an important task for future research to uncover the role of these enzymes. UbiquitinUbiquitin, a small protein of 76 amino acids acting as a tag in post-translational modification of proteins, is absolutely conserved in vertebrates and higher plants, and only two or three amino acid residues are different even among animals, plants, and fungi [22]. The high conservatism renders ubiquitin interchangeable and universal in different species [23]. Ubiquitin is a β-grasp fold protein consisting of a 3.5-turn α-helix, a short 3 10 helix against a five-strand mixed β-sheet and seven reverse turns [24]. Ubiquitin possesses two hydrophobic surfaces. One surface consists of Ile44, Leu8, Val70, and His68 [25], and the other focuses on Ile36 that can be recognized by HECT (Homology to E6-AP C terminus) E3s, DUBs (Deubiquitinating enzymes), and UBDs (Ubiquitin binding domains) [26][27][28]. Ubiquitin contains seven lysine residues, including Lys-6, Lys-11, Lys-27, Lys-29, Lys-33, Lys-48, Lys-63 (K6, K11, K27, K29, K33, K48, and K63, respectively) [29,30]. Six of the seven Lys linkages (with a preference for Lys-48>Lys-63>Lys-11>>>Lys-33/Lys-29/Lys-6) were detected in A. thaliana [31,32]. Any one of the seven lysine residues or N-terminal Met1 residues in ubiquitin is likely to be involved in ubiquitin chain formation in vivo, and different ubiquitin linkages lead to the formation of different types of ubiquitin chains and induce diverse molecular signals in the cell [29,[33][34][35][36]. Different ways of linking ubiquitin chains and substrates result in distinct fates of the substrates. It is well-known that K48-linked chains are mediators signaling proteasom...

Beyond K48 and K63: non-canonical protein ubiquitination

“…Recently, UBC22 has been suggested to play a major role in many cellular processes [ 76 ], probably through its interactions with different E3s. Given that the number of E2s is roughly the same in human and Arabidopsis genomes (~ 40) [ 77 ] but E3s are about two and a half times more abundant in plants (~ 600 in the human genome but over 1,400 in A. thaliana [ 77 ]), one can assume that the UBC22-mediated K11-linked conjugation may be a much more common platform of the Ub landscape in plants than in humans.…”

Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery

“…Substrates of the ERAD pathways are marked with ubiquitin chain with the help of ubiquitin-conjugating enzymes (E1, E2, and E3). After ubiquitination, the tagged protein is identified by 26S proteasome (RPN1, RPN10, and RPN13), deubiquitinated RPN11 (PSMD14), and further degraded, this pathway is important for the degradation of ERAD aberrant protein [ 76 , 77 , 78 , 79 ].…”

“…E3 ligases are binds with both E2 and substrates. In most cases, E3 act as a scaffold to bring together the E2 and substrate; this process allows the transfer of ubiquitin moiety from E2 to the substrate [ 77 , 79 , 83 , 84 , 85 , 86 ].…”

Arabidopsis Ubiquitin-Conjugating Enzymes UBC7, UBC13, and UBC14 Are Required in Plant Responses to Multiple Stress Conditions

“…Since the E2s are required in the transfer of Ub to a substrate and are also important in determining the length and linkage specificity of a Ub chain and reside selection on a substrate [ 5 ], it is conceivable that plant stress responses would require the involvement of at least some E2s. Experimental evidence has implicated some plant E2 genes in the stress responses [ 12 ]. It has been shown that many of the genes encoding the putative E2 enzymes in rice and potato genomes are induced by stresses such as salt and cold as well as by abscisic acid (ABA) [ 13 , 14 ].…”