PXD021404 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Pathway Analysis of Dominant CHIP E3 Ligase-Dependent Protein Steady State Changes Highlight a Role in Neuronal Cell Membrane Integrity Linked to the Actin Cytoskeleton |
Description | Functional 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. |
HostingRepository | PRIDE |
AnnounceDate | 2021-07-29 |
AnnouncementXML | Submission_2021-07-29_02:35:57.016.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Lenka Hernychova |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | TripleTOF 5600 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-10 07:16:47 | ID requested | |
⏵ 1 | 2021-07-29 02:35:57 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, neurons, proteomics, mass spectrometry, SWATH |
Contact List
Prof. Kathryn Ball |
contact affiliation | Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XR Edinburgh, Scotland, United Kingdom |
contact email | Kathryn.Ball@ed.ac.uk |
lab head | |
Lenka Hernychova |
contact affiliation | Masaryk Memorial Cancer Institute |
contact email | hernychova@seznam.cz |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021404
- Label: PRIDE project
- Name: Pathway Analysis of Dominant CHIP E3 Ligase-Dependent Protein Steady State Changes Highlight a Role in Neuronal Cell Membrane Integrity Linked to the Actin Cytoskeleton