PXD027750

PXD027750 is an original dataset announced via ProteomeXchange.

Title	VCP D1 ATPase activation enhances both autophagic and proteasomal neurotoxic protein clearance
Description	Autophagy upregulation enhances the clearance of various neurotoxic proteins and ameliorates their toxicities in disease models. Thus, autophagy activators may have therapeutic utility. Here, we have identified the essential protein VCP/p97 as a target of the autophagy-inducing molecule SMER28, providing a mechanism for a molecule that has shown promising results in animal models of neurodegeneration. SMER28 stimulates VCP D1 ATPase activity to activate autophagy by enhancing interactions of PI3K complex components to increase PI(3)P production and consequent autophagosome formation. Interestingly, SMER28-mediated increase in VCP D1 ATPase activity also enhances degradation of short-lived misfolded and aggregate-prone proteins through the ubiquitin-proteasome system (UPS). We further show that another recently described activator of VCP induces autophagy and UPS flux in a comparable manner, providing additional evidence that targeting VCP D1 ATPase domain could be a useful approach for clearance of aggregate-prone proteins by both autophagy-lysosome and proteasomal routes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:38:20.939.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nigel Beaton
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 10:00:30	ID requested
1	2022-07-15 13:25:31	announced
2	2023-11-14 08:52:11	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 05:38:21	announced	2024-10-22: Updated project metadata.

10.1038/S41467-022-31905-0;

submitter keyword: Beclin 1, ATPase,SMER28, Autophagy, Ubiquitin-proteasome system, limited proteolysis, LiP-MS, Neurodegeneration, VCP, Protein Quality Control

David C. Rubinsztein
contact affiliation	Professor of Molecular Neurogenetics CIMR Deputy Director Cambridge Institute of Medical Research (CIMR) University of Cambridge
contact email	dcr1000@cam.ac.uk
lab head
Nigel Beaton
contact affiliation	Biognosys AG
contact email	nigel.beaton@biognosys.com
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/2022/07/PXD027750

PRIDE project URI

• PRIDE
  1. PXD027750
     1. Label: PRIDE project
     2. Name: VCP D1 ATPase activation enhances both autophagic and proteasomal neurotoxic protein clearance