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PXD042585

PXD042585 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects
DescriptionCD137 (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.
HostingRepositoryPRIDE
AnnounceDate2024-05-24
AnnouncementXMLSubmission_2024-05-24_02:49:03.332.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD042585
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSergio Ciordia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 240
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-31 10:29:58ID requested
12024-05-24 02:49:04announced
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 affiliationCentro de Investigación Médica Aplicada (CIMA), Clínica Universidad de Navarra (CUN)
contact emailimelero@unav.es
lab head
Sergio Ciordia
contact affiliationSpanish National Center for Biotechnology
contact emailsciordia@cnb.csic.es
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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