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PXD021404

PXD021404 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePathway Analysis of Dominant CHIP E3 Ligase-Dependent Protein Steady State Changes Highlight a Role in Neuronal Cell Membrane Integrity Linked to the Actin Cytoskeleton
DescriptionFunctional integrity of the E3-ubiquitin ligase CHIP is essential for healthy aging in the brain. By virtue of its association with the core molecular chaperone machinery, studies into the physiological role(s) of CHIP have been dominated by its involvement in the quality control and degradation of unfolded, aggregated and/or mutated proteins. To elucidate the dominant CHIP-dependent changes in protein steady state levels in human neurons we conducted an unbiased proteomic analysis in genetically engineered wild-type and CHIP knockout iPSC-derived cortical neurons. Rather than a broad effect on protein homeostasis, pathway analysis highlighted a focused cohort of CHIP-responsive proteins involved in actin cytoskeleton signalling and membrane integrity. In support of the pathway analysis CHIP KO cell-lines had enhanced sensitivity to mechanical and chemical membrane damage. Consistent with recent studies on the identification of a non-canonical HSP-independent E3-activity for CHIP, the lack of general quality control defects in knock-out cells suggests that the major readout of CHIP function in cortical neurons is the regulation of native folded substrates involved in maintaining cellular ‘health’. Thus, CHIP-mediated regulation of the of cytoskeletal- and membrane-related proteins is likely to make a vital contribute to the neuroprotective activity of CHIP.
HostingRepositoryPRIDE
AnnounceDate2021-07-29
AnnouncementXMLSubmission_2021-07-29_02:35:57.016.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLenka Hernychova
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 5600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-10 07:16:47ID requested
12021-07-29 02:35:57announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, neurons, proteomics, mass spectrometry, SWATH
Contact List
Prof. Kathryn Ball
contact affiliationInstitute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XR Edinburgh, Scotland, United Kingdom
contact emailKathryn.Ball@ed.ac.uk
lab head
Lenka Hernychova
contact affiliationMasaryk Memorial Cancer Institute
contact emailhernychova@seznam.cz
dataset submitter
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Dataset FTP location
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