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PXD034712-2

PXD034712 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCompounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
DescriptionEnhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington’s disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:57:07.863.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRobin Antrobus
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetic acid derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-20 01:50:49ID requested
12022-07-15 14:59:50announced
22023-11-14 08:57:08announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Beclin 1, ATPase,SMER28, Autophagy, Ubiquitin-proteasome system, Neurodegeneration, VCP, Protein Quality Control
Contact List
David C. Rubinsztein
contact affiliationDepartment of Medical Genetics, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, United Kingdom
contact emaildcr1000@cam.ac.uk
lab head
Robin Antrobus
contact affiliationCIMR medicine
contact emailpra29@cam.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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