PXD042585 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-31 10:29:58 | ID requested | |
⏵ 1 | 2024-05-24 02:49:04 | announced | |
Publication List
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; |
Keyword List
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 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042585
- Label: PRIDE project
- Name: CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects