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PXD028680-1

PXD028680 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-kB signaling in activated T cells
DescriptionT cell activation initiates protective adaptive immunity, but counterbalancing mechanisms are critical to prevent overshooting responses and to maintain immune homeostasis. The CARD11-BCL10-MALT1 (CBM) complex bridges T cell receptor engagement to canonical NF-B signaling and MALT1 protease activation. Here we show that the A20-binding inhibitor of NF-B ABIN-1 (also termed TNIP1) is modulating the suppressive function of A20 in T cells. Using quantitative mass -spectrometry, we identified ABIN-1 as an interactor of the CBM signalosome in activated T cells, which similar to A20 counteracts inducible activation of human primary and Jurkat T cells. However, while A20 overexpression silences CBM complex-triggered NF-B and MALT1 protease activation independent of ABIN-1, the negative regulatory function of ABIN-1 depends on A20. We show that the suppressive function of A20 in T cells relies on ubiquitin binding through the C-terminal zinc finger (ZnF)4/7 motifs, but does not involve the deubiquitinating activity of the OTU domain. Mechanistic studies reveal that the A20/ABIN-1 module is recruited to the CBM complex via A20 ZnF4/7 and that proteasomal degradation of A20 and ABIN-1 releases the initial CBM complex from the negative impact of both regulators. ABIN-1 degradation involves K48-polyubiquitination, which is promoted by A20 ZnF4/7. Further, after pro-longed T cell stimulation ABIN-1 antagonizes MALT1-catalyzed cleavage of newly synthesized A20 and thereby impairs sustained CBM complex signaling. Taken together, interdependent post-translational mechanisms are tightly controlling expression and activity of the A20/ABIN-1 silencing module and the cooperative action of both negative regulators is critical to balance CBM complex signaling and T cell activation.
HostingRepositoryPRIDE
AnnounceDate2022-01-30
AnnouncementXMLSubmission_2022-01-30_13:34:42.127.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMario Oroshi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-21 10:10:39ID requested
12022-01-30 13:34:42announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Adaptive Immunity, T Cell Signaling, Immune Suppression, A20, ABIN1, CBM complex, proteomics, mass spectrometry, IP-MS
Contact List
Matthias Mann
contact affiliationDepartment of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Germany
contact emailmmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliationProteomics
contact emailoroshi@biochem.mpg.de
dataset submitter
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