PXD054393

PXD054393 is an original dataset announced via ProteomeXchange.

Title	B7-H4 post-translational modifications
Description	B7-H4 functions as an immune checkpoint in the tumor microenvironment (TME). However, the post-translational modification (PTM) of B7-H4 and its translational potential in cancer remains incompletely understood. We found that ZDHHC3, a zinc finger DHHC-type palmitoyltransferase, palmitoylates B7-H4 at Cys130 in breast cancer cells, preventing its lysosomal degradation and sustaining B7-H4-mediated immunosuppression. Knockdown of ZDHHC3 in tumors resulted in robust anti-tumor immunity and reduced tumor progression in murine models. Moreover, abemaciclib, a CDK4/6 inhibitor, primed lysosome activation and promoted lysosomal degradation of B7-H4 independently of the tumor cell cycle. Treatment with abemaciclib resulted in T cell activation and mitigated B7-H4-mediated immune suppression via inducing B7-H4 degradation in preclinical tumor models. Thus, B7-H4 palmitoylation is an undocumented PTM controlling B7-H4 protein stability and abemaciclib may be repurposed to enhance B7-H4 degradation, thereby treating patients with B7-H4+ tumors.
HostingRepository	PRIDE
AnnounceDate	2025-02-14
AnnouncementXML	Submission_2025-02-14_04:16:30.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weiping Zou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	palmitoylated residue; phosphorylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-30 06:53:33	ID requested
⏵ 1	2025-02-14 04:16:31	announced

Dataset with its publication pending

submitter keyword: lysosome, palmitoylation, breast cancers, abemaciclib,B7-H4

Weiping Zou
contact affiliation	Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
contact email	wzou@umich.edu
lab head
Weiping Zou
contact affiliation	University of Michigan
contact email	wzou@umich.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/2025/02/PXD054393

PRIDE project URI

• PRIDE
  1. PXD054393
     1. Label: PRIDE project
     2. Name: B7-H4 post-translational modifications