Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation
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Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation. / Parker, Benjamin L; Kiens, Bente; Wojtaszewski, Jørgen; Richter, Erik A.; James, David E.
I: F A S E B Journal, Bind 34, Nr. 4, 2020, s. 5906-5916.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation
AU - Parker, Benjamin L
AU - Kiens, Bente
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
AU - James, David E
N1 - © 2020 The University of Sydney. The FASEB Journal © 2020 Federation of American Societies for Experimental Biology.
PY - 2020
Y1 - 2020
N2 - The maintenance of muscle function is extremely important for whole body health and exercise is essential to this process. The ubiquitin-proteasome system (UPS) is required for muscle adaptation following exercise but little is known about acute posttranslational regulation and proteome remodeling during and after high-intensity exercise. Here, we used quantitative proteomics to study ubiquitin signaling dynamics in human skeletal muscle biopsies from healthy males before, during, and after a single bout of high-intensity exercise. Exercise resulted in a marked depletion of protein ubiquitylation in the vastus lateralis muscle consistent with proteasome activation. This was also associated with acute posttranslational modification of protein abundance. Integration of these data with phosphoproteomics identified co-regulated proximal modifications suggesting a cross talk between phosphorylation and ubiquitylation. We also identified additional protein modification cross talk and showed acute activation of protein NEDDylation. In vitro experiments revealed that cAMP-dependent activation of the proteasome requires NEDD8, an ubiquitin-like protein involved in protein NEDDylation, to maintain cellular protein ubiquitylation levels. Our data reveal the complexity of ubiquitin signaling and proteome remodeling in muscle during and after high-intensity exercise. We propose a model whereby exercise and the resulting cAMP signaling activate both the proteasome and ubiquitylation via NEDDylation to rapidly remove potentially damaged proteins.
AB - The maintenance of muscle function is extremely important for whole body health and exercise is essential to this process. The ubiquitin-proteasome system (UPS) is required for muscle adaptation following exercise but little is known about acute posttranslational regulation and proteome remodeling during and after high-intensity exercise. Here, we used quantitative proteomics to study ubiquitin signaling dynamics in human skeletal muscle biopsies from healthy males before, during, and after a single bout of high-intensity exercise. Exercise resulted in a marked depletion of protein ubiquitylation in the vastus lateralis muscle consistent with proteasome activation. This was also associated with acute posttranslational modification of protein abundance. Integration of these data with phosphoproteomics identified co-regulated proximal modifications suggesting a cross talk between phosphorylation and ubiquitylation. We also identified additional protein modification cross talk and showed acute activation of protein NEDDylation. In vitro experiments revealed that cAMP-dependent activation of the proteasome requires NEDD8, an ubiquitin-like protein involved in protein NEDDylation, to maintain cellular protein ubiquitylation levels. Our data reveal the complexity of ubiquitin signaling and proteome remodeling in muscle during and after high-intensity exercise. We propose a model whereby exercise and the resulting cAMP signaling activate both the proteasome and ubiquitylation via NEDDylation to rapidly remove potentially damaged proteins.
KW - Faculty of Science
KW - Exercise
KW - Human skeletal muscle
KW - Isotopic labeling
KW - Mass spectrometry
KW - NEDD8
KW - Proteomics
KW - Ubiquitin
U2 - 10.1096/fj.202000075R
DO - 10.1096/fj.202000075R
M3 - Journal article
C2 - 32141134
VL - 34
SP - 5906
EP - 5916
JO - F A S E B Journal
JF - F A S E B Journal
SN - 0892-6638
IS - 4
ER -
ID: 237514915