Expression of SUMO enzymes is fiber type dependent in skeletal muscles and is dysregulated in muscle disuse

Abstract

Abbreviations: ISG15, interferon-stimulated gene 15; MTCO1, mitochondria complex 1; NEDD8, neural precursor cell expressed, developmentally down-regulated 8; PIASs, Protein inhibitor of activated STAT superfamily; PTM(s), Post-translational modification(s); RANBP2, RAN Binding Protein 2; SAE1/2, SUMO activating enzyme subunits ½; SENP(s), Sentrin-specific proteases; SUMO, Small Ubiquitin-like Modifier; SUMO E1, SUMO-activating enzyme E1; SUMO E2, SUMO-conjugating enzyme E2; SUMO E3, SUMO ligase E3; UBC9, Ubiquitin conjugating enzyme 9; ZNF451, Zinc Finger Protein 451. Abstract SUMOylation is a dynamic, reversible, enzymatic drug-targetable post-translational modification (PTM) reaction where the Small Ubiquitin-like Modifier (SUMO) moieties are attached to proteins. This reaction regulates various biological functions like cell growth, differentiation, and it is crucial for maintaining organ homeostasis.However, the actions of SUMO in skeletal muscle pathophysiology are still not investigated. In this study, we quantified the abundance of the SUMO enzymes and determined the distribution of SUMOylated proteins along the fibers of nine different muscles. We find that skeletal muscles contain a distinctive group of SUMO enzymes and SUMOylated proteins in relation to their different metabolism, functions, and fiber type composition. In addition, before the activation of protein degradation pathways, this unique set is quickly altered in response to muscle sedentariness.Finally, we demonstrated that PAX6 acts as an upstream regulator of the SUMO conjugation reaction, which can become a potential therapeutic marker to prevent muscle diseases generated by inactivity.

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“…In human myofibers, exercise within 15 to 30 min could cause the elevation of nuclear SUMO-1 localization . Namuduri et al reported the expression of SUMO in disordered muscle was dysregulated. Therefore, YPLP could increase the level of SUMO modification in the Nup358 complex to improve muscle movement.…”

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“…Once the dynamic balance between SUMO and de-SUMO is broken, it can lead to tumor occurrence. Sumoylation is catalyzed by E1, E2 and E3 enzymes, while desumoylation is performed by SUMOspecific proteases (SENPs) (18). Human desumoylation proteases SENPs, including SENP1, SENP 2, SENP 3, SENP 5, SENP 6 and SENP 7, play a key role in this pathway (19).…”