PXD040473

PXD040473 is an original dataset announced via ProteomeXchange.

Title	Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy
Description	Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as a new pathway for p53 regulation. Like Mdm2 (Mouse double minute 2), VPRBP is a potent repressor of p53 but VPRBP stability is controlled by USP2. Interestingly, the USP2-VPRBP axis is also involved in PD-L1 (programmed death-ligand 1) regulation. Strikingly, in immunocompetent mouse models, the combination of a small-molecule USP2 inhibitor and anti-PD1 monoclonal antibody leads to complete regression of the tumors expressing wild-type p53. In contrast to Mdm2, knockout of the USP2 gene in mice has no obvious effect in normal tissues. Moreover, no obvious toxicity is observed upon the USP2 inhibitor treatment in vivo as Mdm2-mediated regulation of p53 remains intact. These data demonstrate that USP2 is a promising target to induce potent tumor suppression without obvious toxicity. Our study reveals a new strategy for p53-based therapy by circumventing the toxicity issue.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:48.360.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD040473
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	huan li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-27 09:40:09	ID requested
1	2023-03-15 05:17:15	announced
2	2023-04-11 02:28:57	announced	2023-04-11: Updated project metadata.
⏵ 3	2023-11-14 08:44:49	announced	2023-11-14: Updated project metadata.

10.6019/PXD040473;

Yi J, Tavana O, Li H, Wang D, Baer RJ, Gu W, Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy. Nat Commun, 14(1):1941(2023) [pubmed]

submitter keyword: PD-1, IRF1, USP2 inhibitors, USP2, VPRBP, PD-L1, Mdm2 and tumor suppressor,p53

Wei Gu
contact affiliation	Department of Pathology and Cell Biology and Institute for Cancer Genetics Herbert Irving Comprehensive Cancer Vagelos College of Physicians & Surgeons Columbia University
contact email	wg8@cumc.columbia.edu
lab head
huan li
contact affiliation	COLUMBIA UNIVERSITY MEDICAL CENTER
contact email	hl2977@cumc.columbia.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/2023/03/PXD040473

PRIDE project URI

• PRIDE
  1. PXD040473
     1. Label: PRIDE project
     2. Name: Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy