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PXD023391

PXD023391 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleASB2 interactome in C2C12 cells
DescriptionUbiquitination is a post-translational protein modification that has been shown to have a range of effects, including regulation of protein function, interaction, localization, and degradation. We have previously shown that the muscle-specific ubiquitin E3 ligase, ASB2β, is down-regulated in models of muscle growth and that overexpression ASB2 is sufficient to induce muscle atrophy. To gain insight into the effects of increased ASB2 expression on skeletal muscle mass and function, we used liquid chromatography coupled to tandem mass spectrometry to investigate ASB2-mediated changes to the skeletal muscle proteome and ubiquitinome, via a parallel analysis of remnant di-Gly-modified peptides. The results show that viral vector-mediated ASB2β overexpression in murine muscles causes progressive muscle atrophy and impairment of force-producing capacity, while ASB2β knockdown induces mild muscle hypertrophy. ASB2β-induced muscle atrophy and dysfunction were associated with the early downregulation of mitochondrial and contractile protein abundance, and the upregulation of proteins involved in proteasome-mediated protein degradation (including other E3 ligases), 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 investigate proteins that interact with ASB2 and, therefore, potential ASB2 targets, Flag-tagged wild type ASB2, and a mutant ASB2 lacking the 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, our studies have identified novel putative ASB2β target substrates that warrant further investigation. These findings provide novel insight into the complexity of proteome and ubiquitinome changes that occur during E3 ligase-mediated skeletal muscle atrophy and dysfunction.
HostingRepositoryPRIDE
AnnounceDate2021-03-18
AnnouncementXMLSubmission_2021-03-18_14:28:07.358.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBenjamin Parker
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-01-04 04:00:01ID requested
12021-03-18 14:28:08announced
Publication List
Goodman CA, Davey JR, Hagg A, Parker BL, Gregorevic P, . Mol Cell Proteomics, 20():100050(2021) [pubmed]
Keyword List
submitter keyword: ASB2, E3 ligase, protein interactions
Contact List
Benjamin Parker
contact affiliationThe University of Melbourne
contact emailben.parker@unimelb.edu.au
lab head
Benjamin Parker
contact affiliationThe University of Melbourne
contact emailben.parker@unimelb.edu.au
dataset submitter
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