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CHIP controls the expression of the neuropeptide precursor protein VGF

ABSTRACT: CHIP is a neuroprotective E3-ubiquitin ligase that supports longevity and healthy ageing. Loss of CHIP function has a major impact on life expectancy in animal models, whilst in humans’ mutations that compromise the E3-ligase activity of CHIP are causative for forms of Spinocerebellar Ataxia (SCA) that are accompanied by cognitive decline and/or dementia. The pathways regulated by CHIP to maintain neuronal health remain to be discovered. Gene-edited neuroblastoma cells were produced and used as a model to study the effects of CHIP loss on the steady state proteome in the absence of proteotoxic stress. Label free quantitative proteomic analysis (SWATH-MS) highlighted VGF, a member of the neuropeptide precursor family of proteins, as being a dominant protein responding to loss of CHIP function. By studying the dependence of VGF expression on CHIP using SILAC and RNA-Seq we have defined a role for the ligase in regulated neuropeptide expression.

INSTRUMENT(S): TripleTOF 5600, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Neuroblast

DISEASE(S): Spinocerebellar Ataxia Type 31

SUBMITTER: Lenka Hernychova

LAB HEAD: Kathryn Ball

PROVIDER: PXD016299 | Pride | 2021-07-29

REPOSITORIES: Pride

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			Action	DRS
	CHIP_KO_1.msf	Msf
	CHIP_KO_1.raw	Raw
	CHIP_KO_2.msf	Msf
	CHIP_KO_2.raw	Raw
	CHIP_KO_3.msf	Msf

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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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LC-MS/MS proteomics analysis of neuronal cells and secretomes with timsTOF Pro

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