Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation

Research output: Contribution to journalJournal articlepeer-review

Standard

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.

In: F A S E B Journal, Vol. 34, No. 4, 2020, p. 5906-5916.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Parker, BL, Kiens, B, Wojtaszewski, J, Richter, EA & James, DE 2020, 'Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation', F A S E B Journal, vol. 34, no. 4, pp. 5906-5916. https://doi.org/10.1096/fj.202000075R

APA

Parker, B. L., Kiens, B., Wojtaszewski, J., Richter, E. A., & James, D. E. (2020). Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation. F A S E B Journal, 34(4), 5906-5916. https://doi.org/10.1096/fj.202000075R

Vancouver

Parker BL, Kiens B, Wojtaszewski J, Richter EA, James DE. Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation. F A S E B Journal. 2020;34(4):5906-5916. https://doi.org/10.1096/fj.202000075R

Author

Parker, Benjamin L ; Kiens, Bente ; Wojtaszewski, Jørgen ; Richter, Erik A. ; James, David E. / Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation. In: F A S E B Journal. 2020 ; Vol. 34, No. 4. pp. 5906-5916.

Bibtex

@article{9741f8d5401c4316b9e42b7ce3951cad,
title = "Quantification of exercise-regulated ubiquitin signaling in human skeletal muscle identifies protein modification cross talk via NEDDylation",
abstract = "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.",
keywords = "Faculty of Science, Exercise, Human skeletal muscle, Isotopic labeling, Mass spectrometry, NEDD8, Proteomics, Ubiquitin",
author = "Parker, {Benjamin L} and Bente Kiens and J{\o}rgen Wojtaszewski and Richter, {Erik A.} and James, {David E}",
note = "{\textcopyright} 2020 The University of Sydney. The FASEB Journal {\textcopyright} 2020 Federation of American Societies for Experimental Biology.",
year = "2020",
doi = "10.1096/fj.202000075R",
language = "English",
volume = "34",
pages = "5906--5916",
journal = "F A S E B Journal",
issn = "0892-6638",
publisher = "Federation of American Societies for Experimental Biology",
number = "4",

}

RIS

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