PXD020040 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ASB2beta-induced changes to the skeletal muscle proteome and ubiquitinome |
Description | Ubiquitination is a post-translational modification that has been shown to have a range of effects, such as regulating protein function, protein:protein interactions, protein localization, and protein abundance by targeting proteins for degradation by the 26S proteasome. We have previously shown that the muscle-specific ubiquitin E3 ligase, ASB2, is down-regulated in models of muscle growth and that overexpression ASB2 is sufficient to induce muscle atrophy. To gain insight into the effect of increased ASB2 expression on skeletal muscle mass and function, we used 2-dimensional nano-ultra-high-performance mass spectrometry to investigate ASB2-induced changes to the mouse skeletal muscle proteome, and whether these were associated with changes in protein ubiquitination. The results show that in vivo recombinant adeno-associated viral vector-mediated ASB2β overexpression induces impaired intrinsic force production and progressive muscle atrophy over 12 weeks, while ASB2 knockdown induces mild muscle hypertrophy. ASB2-induced muscle atrophy and dysfunction were associated with the early down regulation of mitochondrial and contractile proteins, and the upregulation of proteins involved in proteasome-mediated protein degradation, protein synthesis and the cytoskeleton/sarcomere. The overexpression ASB2β also resulted in marked changes in protein ubiquitination, however, there was no simple relationship between changes in ubiquitination status and protein abundance. To gain insights into proteins that interact with ASB2, and potential ASB2 targets, in muscle cells, flag-tagged wild type ASB2, and a mutant ASB2 with a deleted C-terminal SOCS box domain (dSOCS) were immunoprecipitated from C2C12 myotubes and subjected to label-free proteomic analysis to determine the ASB2 interactome. ASB2β was found to interact with a range of cytoskeletal and nuclear proteins. When combined with the in vivo ubiquitinomic data, we identified several novel potential ASB2β target substrates that await further investigation. Overall, this study reveals for the first time the complexity of changes to the proteome and ubiquitinome during E3 ligase-mediated skeletal muscle atrophy and dysfunction. |
HostingRepository | PRIDE |
AnnounceDate | 2021-03-18 |
AnnouncementXML | Submission_2021-03-18_14:32:17.477.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Benjamin Parker |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-26 03:17:03 | ID requested | |
⏵ 1 | 2021-03-18 14:32:18 | announced | |
2 | 2024-10-22 05:20:11 | announced | 2024-10-22: Updated project metadata. |
Publication List
Goodman CA, Davey JR, Hagg A, Parker BL, Gregorevic P, . Mol Cell Proteomics, 20():100050(2021) [pubmed] |
Keyword List
submitter keyword: skeletal muscle, ubiquitin, adeno-associated virus |
Contact List
Benjamin Parker |
contact affiliation | The University of Melbourne |
contact email | ben.parker@unimelb.edu.au |
lab head | |
Benjamin Parker |
contact affiliation | The University of Melbourne |
contact email | ben.parker@unimelb.edu.au |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020040
- Label: PRIDE project
- Name: ASB2beta-induced changes to the skeletal muscle proteome and ubiquitinome