PXD042878

PXD042878 is an original dataset announced via ProteomeXchange.

Title	Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation
Description	Most eukaryotic proteins are degraded by the 26S proteasome after modification with a polyubiquitin chain. Substrates lacking unstructured segments cannot be degraded directly and require prior unfolding by the Cdc48 ATPase (p97 or VCP in mammals) in complex with its ubiquitin-binding partner Ufd1-Npl4 (UN). Here, we use purified yeast components to reconstitute Cdc48-dependent degradation of well-folded model substrates by the proteasome. We show that a minimal system consists of the 26S proteasome, the Cdc48-UN ATPase complex, the proteasome cofactor Rad23, and the Cdc48 cofactors Ubx5 and Shp1. Rad23 and Ubx5 stimulate polyubiquitin binding to the 26S proteasome and the Cdc48-UN complex, respectively, allowing these machines to compete for substrates before and after their unfolding. Shp1 stimulates protein unfolding by the Cdc48-UN complex, rather than substrate recruitment. In vivo experiments confirm bidirectional substrate shuttling between the 26S proteasome and Cdc48 ATPase and identify proteins that require both machines for their degradation.
HostingRepository	PRIDE
AnnounceDate	2024-02-23
AnnouncementXML	Submission_2024-02-23_08:50:45.742.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-11 13:54:11	ID requested
⏵ 1	2024-02-23 08:50:46	announced

Dataset with its publication pending

submitter keyword: ERAD, AAA ATPase, protein degradation, ubiquitin, Cdc48, shuttling factor, p97,Proteasome, protein unfolding

Tom A. Rapoport
contact affiliation	Harvard Medical School Department of Cell Biology Boston MA, USA
contact email	tom_rapoport@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042878
     1. Label: PRIDE project
     2. Name: Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation