PXD071054

PXD071054 is an original dataset announced via ProteomeXchange.

Title	Systematic characterization of cancer-associated SPOP mutants reveals novel and reprogrammable degradative activities
Description	Speckle-type POZ protein (SPOP) functions as the substrate adaptor of the Cullin3-RING ligase (CRL3) complex and is recurrently mutated in multiple cancer types. Among these, F102C and F133L are frequent prostate cancer mutations within the substrate-binding domain, yet their biochemical consequences remain incompletely understood. Using quantitative proteomics, we show that SPOP-F133L, unlike SPOP-F102C, retains degradative activity toward the nuclear basket proteins NUP153 and TPR, indicating substrate-dependent loss-of-function. Moreover, SPOP-F133L induces partial down-regulation of p53 through a CRL-dependent, post-translational mechanism, revealing a potential neo-substrate relationship. Finally, we demonstrate that both SPOP-F102C and SPOP-F133L support targeted protein degradation (TPD) in an engineered cellular system. These findings define the degradative capacities of SPOP mutants and highlight opportunities to repurpose these variants as mutant-selective E3 ligases for therapeutic applications.
HostingRepository	PRIDE
AnnounceDate	2025-12-17
AnnouncementXML	Submission_2025-12-17_07:17:12.367.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoyu Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-21 12:45:25	ID requested
⏵ 1	2025-12-17 07:17:12	announced

10.1002/CBIC.202500914;

submitter keyword: E3 ligase, Targeted protein degradation, Proteomics

Xiaoyu Zhang
contact affiliation	Northwestern University, Department of Chemistry
contact email	zhang@northwestern.edu
lab head
Xiaoyu Zhang
contact affiliation	Northwestern University
contact email	zhang@northwestern.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071054
     1. Label: PRIDE project
     2. Name: Systematic characterization of cancer-associated SPOP mutants reveals novel and reprogrammable degradative activities