PXD021404

PXD021404 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-10 07:16:47	ID requested
⏵ 1	2021-07-29 02:35:57	announced

Dataset with its publication pending

submitter keyword: Human, neurons, proteomics, mass spectrometry, SWATH

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/07/PXD021404

PRIDE project URI

• PRIDE
  1. PXD021404
     1. Label: PRIDE project
     2. 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