PXD053581

PXD053581 is an original dataset announced via ProteomeXchange.

Title	p97/VCP is required for piecemeal autophagy of aggresomes
Description	Metazoan cells adapt to the exhaustion of protein quality control (PQC) systems by sequestering aggregation-prone proteins in large, pericentriolar structures termed aggresomes. Defects in both, aggresome formation and clearance affect proteostasis and have been linked to neurodegenerative diseases, but aggresome clearance pathways are still underexplored. Here we show that aggresomes comprising endogenous proteins are cleared via selective autophagy requiring the cargo receptor TAX1BP1. TAX1BP1 proximitomes revealed the presence of various PQC systems at aggresomes, including Hsp70 chaperones, the 26S proteasome and the ubiquitin-selective unfoldase p97/VCP. We show that Hsp70 and p97/VCP with its cofactors UFD1-NPL4 and FAF1 play key roles in aggresome disassembly, whereas the 26S proteasome is not strictly required. We identified aggresomal client proteins that are degraded via different routes, some in a p97-dependent manner via aggrephagy. Upon acute inhibition of p97/VCP, aggresomes failed to disintegrate and were not incorporated into autophagosomes despite the presence of factors critical for aggrephagosome formation, including TAX1BP1, p62/SQSTM1, and WIPI2. We conclude that the p97/VCP-mediated removal of ubiquitylated aggresomal clients is essential for the disintegration and subsequent piecemeal autophagy of aggresomes.
HostingRepository	PRIDE
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-14_07:18:45.809.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julian Bender
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-02 16:39:43	ID requested
⏵ 1	2025-04-14 07:18:46	announced

Dataset with its publication pending

submitter keyword: aggrephagy, proximity proteomics, TurboID, protein quality control, TAX1BP1,p97/VCP, piecemeal autophagy

Bettina Warscheid
contact affiliation	Chair of Biochemistry II, Theodor Boveri-Institute, Biocenter, University of Würzburg, Würzburg, Germany
contact email	bettina.warscheid@uni-wuerzburg.de
lab head
Julian Bender
contact affiliation	University of Wuerzburg Chair of Biochemistry II Am Hubland 97074 Würzburg
contact email	julian.bender@uni-wuerzburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053581
     1. Label: PRIDE project
     2. Name: p97/VCP is required for piecemeal autophagy of aggresomes