PXD022399

PXD022399 is an original dataset announced via ProteomeXchange.

Title	Small-molecule degraders of SUMO1 induce the protein ubiquitination and degradation through CAPRIN1-CUL1-FBXO42 ubiquitin ligase for cancer therapySmall-molecule degraders of SUMO1 induce the protein ubiquitination and degradation through CAPRIN1-CUL1-FBXO42 ubiquitin ligase for cancer therapy
Description	Targeted protein degradation has been a long sought, but elusive, strategy for discovery of small-molecule degraders that activate E3 ubiquitin ligase-mediated ubiquitination and degradation of targeted proteins in cancer cells. Here, we report a cancer cell-based drug screen in the discovery of small-molecule degraders of SUMO1 that has been an otherwise undruggable protein. Genome-scale CRISPR-CAS9 screen combined with compound pulldown proteomics identified the binding partner CAPRIN1 and the SUMO1 substrate receptor FBXO42 of CUL1 E3 ligase. Upon binding of CAPRIN1, SUMO1 degraders induce CAPRIN1-FBXO42 interaction and recruitment of SUMO1 to the CAPRIN1-CUL1-FBXO42 E3 ligase for SUMO1 ubiquitination and degradation in cancer but not normal cells. SUMO1 degraders exhibit drug-like pharmacokinetics and profound anticancer activity against various cancer models. This cancer cell-based drug screen provides an alternative approach for the discovery of new small-molecule degraders of oncoproteins as a new generation of anticancer drugs.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:16:28.964.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022399
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-06 01:39:10	ID requested
1	2022-10-13 14:20:20	announced
⏵ 2	2023-11-14 07:16:29	announced	2023-11-14: Updated project metadata.

10.6019/PXD022399;

Bellail AC, Jin HR, Lo HY, Jung SH, Hamdouchi C, Kim D, Higgins RK, Blanck M, le Sage C, Cross BCS, Li J, Mosley AL, Wijeratne AB, Jiang W, Ghosh M, Zhao YQ, Hauck PM, Shekhar A, Hao C, Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors. Sci Transl Med, 13(615):eabh1486(2021) [pubmed]

submitter keyword: cancer, CAPRIN1, FBXO42, CUL1 E3 ligase, HCT116, ubiquitination, SUMO1,CRISPR-CAS9,E3 ubiquitin ligase, sumoylation

Amber Mosley
contact affiliation	Associate Professor of Biochemistry & Molecular Biology, Director Proteomics Core, Indiana University School of Medicine
contact email	almosley@iu.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
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/2022/10/PXD022399

PRIDE project URI

• PRIDE
  1. PXD022399
     1. Label: PRIDE project
     2. Name: Small-molecule degraders of SUMO1 induce the protein ubiquitination and degradation through CAPRIN1-CUL1-FBXO42 ubiquitin ligase for cancer therapySmall-molecule degraders of SUMO1 induce the protein ubiquitination and degradation through CAPRIN1-CUL1-FBXO42 ubiquitin ligase for cancer therapy