PXD028680

PXD028680 is an original dataset announced via ProteomeXchange.

Title	A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-kB signaling in activated T cells
Description	T 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.
HostingRepository	PRIDE
AnnounceDate	2022-01-30
AnnouncementXML	Submission_2022-01-30_13:34:42.127.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-21 10:10:39	ID requested
⏵ 1	2022-01-30 13:34:42	announced

Dataset with its publication pending

submitter keyword: Adaptive Immunity, T Cell Signaling, Immune Suppression, A20, ABIN1, CBM complex, proteomics, mass spectrometry, IP-MS

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028680
     1. Label: PRIDE project
     2. Name: A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-kB signaling in activated T cells