The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

Abstract

In recent years, the ubiquitin-proteasome system (UPS) has emerged as an important regulator of stem cell function. Here we review recent findings indicating that UPS also plays critical roles in the biology of satellite cells, the muscle stem cell responsible for its maintenance and regeneration. While we focus our attention on the control of key transcriptional regulators of satellite cell function, we briefly discuss early studies suggesting the UPS participates more broadly in the regulation of satellite cell stemness and regenerative capacity.

Role of the Ubiquitin Ligase RNF149 in the Development of Rat Neonatal Gonocytes

“…The ubiquitin proteasome system has been widely studied due to its multiple functions in regulating protein degradation, kinase activation, DNA repair, trafficking, translation, and signal pathway activation (12)(13)(14)(15)(16)(17). In addition, among the three key enzymes of the UPS, E3 ligases play the most important role as they provide specificity to the entire process (14).…”

“…The ubiquitin proteasome system has been widely studied due to its multiple functions in regulating protein degradation, kinase activation, DNA repair, trafficking, translation, and signal pathway activation (12)(13)(14)(15)(16)(17). In addition, among the three key enzymes of the UPS, E3 ligases play the most important role as they provide specificity to the entire process (14). RING-type E3 ligases have been reported to be important regulators in many diseases, such as Mdm2, that can ubiquitinate P53 (26), and Skp2, that can degrade c-Myc (27), thus their involvement in various disease states.…”

“…UPS is the main pathway by which proteins are degraded in eukaryotes, involving a succession of enzymatic reactions involved in the attachment of an ubiquitin chain to a substrate protein targeted for degradation, including an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase (12,13). UPS activity regulates a variety of developmental and biological functions, such as myogenesis, bone formation and immune function (14)(15)(16). During the ubiquitination process, the E1 activating enzyme activates the ubiquitin molecule which is then transferred to the E2 conjugating enzyme and finally to an E3 ligase.…”

Intersection of the Ubiquitin–Proteasome System with Oxidative Stress in Cardiovascular Disease

“…It is generally accepted that activated Ub is gradually transferred to its target protein: Ub attaches to a cysteine residue of E1 Ub-activating enzyme in an ATP-dependent reaction, and the activated Ub transfers to a cysteine residue of E2 Ub-conjugating enzyme, which in turn transfers the Ub to a lysine residue of the substrate protein via an E3 ligase. E3 enzymes, as the critical components in the ubiquitination cascade, can be classified into three main groups according to the presence of the (1) Really Interesting New Gene-finger (RING) domain (comprising the largest group, which directly catalyzes the transfer of Ub), (2) homologous to the E6AP carboxyl terminus (HECT) domain (which accepts Ub from E2 Ub-conjugating enzyme), and (3) RING-in-Between-RING (RBR) E3 ligases (with the common features of RING and HECT E3 groups) [ 21 ]. The structures of these domains are summarized schematically in Figure 2 [ 22 ].…”

“…Ubiquitinated proteins are degraded after reaching the 26S proteasome ( Figure 2 ) [ 23 ]. With two terminal α-subunit rings and two middle β-subunit rings, the 20S proteasome forms a core complex that combines with the 19S proteosome, a two-cap-like regulated structure consisting of the ATP-dependent 26S proteasome [ 21 ]. The polyubiquitin proteolytic signal allows the 26S proteasome to recognize a large variety of protein substrates, which can realize the function of the UPS [ 24 ].…”