Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell

DISEASE(S): Neurodegenerative Disease

SUBMITTER: Lenka Hernychova

LAB HEAD: Prof. Kathryn Ball

PROVIDER: PXD021404 | Pride | 2021-07-29

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	SWATH_iPSC_CHIP_KO_1_11stanalysis.wiff	Wiff
	SWATH_iPSC_CHIP_KO_1_11stanalysis.wiff.scan	Wiff
	SWATH_iPSC_CHIP_KO_1_12ndanalysis.wiff	Wiff
	SWATH_iPSC_CHIP_KO_1_12ndanalysis.wiff.scan	Wiff
	SWATH_iPSC_CHIP_KO_1_21stanalysis.wiff	Wiff

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Dataset Information

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

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