PXD042585

PXD042585 is an original dataset announced via ProteomeXchange.

Title	CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects
Description	CD137 (4-1BB) is a member of the TNFR family that mediates potent T-cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies. CD137 agonists attain immunotherapeutic antitumor effects in cancer mouse models and multiple agents of this kind are undergoing clinical trials. We show that cIAP1 and cIAP2 are physically associated with the CD137-signaling complex. Moreover, cIAPs are required for CD137 signaling towards the NF-κB and MAPK pathways and for costimulation of human and mouse T lymphocytes. Functional evidence was substantiated with SMAC-mimetics that trigger cIAPs degradation and by transfecting cIAP dominant-negative variants. Antitumor effects of agonist anti-CD137 mAbs are critically dependent on the integrity of cIAPs in cancer mouse models and cIAPs are also required for signaling from CARs encompassing CD137’s cytoplasmic tail.
HostingRepository	PRIDE
AnnounceDate	2024-05-24
AnnouncementXML	Submission_2024-05-24_02:49:03.332.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042585
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Ciordia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-31 10:29:58	ID requested
⏵ 1	2024-05-24 02:49:04	announced

Glez-Vaz J, Azpilikueta A, Ochoa MC, Olivera I, Gomis G, Cirella A, Luri-Rey C, Á, lvarez M, P, é, rez-Gracia JL, Ciordia S, Eguren-Santamaria I, Alexandru R, Berraondo P, de Andrea C, Teijeira Á, Corrales F, Zapata JM, Melero I, CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects. Sci Adv, 9(33):eadf6692(2023) [pubmed]

10.1126/sciadv.adf6692;

10.6019/PXD042585;

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: 4-1BB, Smac Mimetic Compounds,CD137, cIAP1, cIAP2, Immunotherapy

Ignacio Melero Bermejo
contact affiliation	Centro de Investigación Médica Aplicada (CIMA), Clínica Universidad de Navarra (CUN)
contact email	imelero@unav.es
lab head
Sergio Ciordia
contact affiliation	Spanish National Center for Biotechnology
contact email	sciordia@cnb.csic.es
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/2024/05/PXD042585

PRIDE project URI

• PRIDE
  1. PXD042585
     1. Label: PRIDE project
     2. Name: CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects