dc.identifier.uri |
http://dx.doi.org/10.15488/12891 |
|
dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/12995 |
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dc.contributor.author |
Yin, Hongli
|
|
dc.contributor.author |
Karayel, Ozge
|
|
dc.contributor.author |
Chao, Ying-Yin
|
|
dc.contributor.author |
Seeholzer, Thomas
|
|
dc.contributor.author |
Hamp, Isabel
|
|
dc.contributor.author |
Plettenburg, Oliver
|
|
dc.contributor.author |
Gehring, Torben
|
|
dc.contributor.author |
Zielinski, Christina
|
|
dc.contributor.author |
Mann, Matthias
|
|
dc.contributor.author |
Krappmann, Daniel
|
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dc.date.accessioned |
2022-11-01T07:04:19Z |
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dc.date.available |
2022-11-01T07:04:19Z |
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dc.date.issued |
2022 |
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dc.identifier.citation |
Yin, H.; Karayel, O.; Chao, Y.-Y.; Seeholzer, T.; Hamp, I. et al.: A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. In: Cellular and molecular life sciences : (CMLS) 79 (2022), Nr. 2, 112. DOI: https://doi.org/10.1007/s00018-022-04154-z |
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dc.description.abstract |
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 NF-κB signaling and MALT1 protease activation. Here, we show that ABIN-1 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. A20 and ABIN-1 counteract inducible activation of human primary CD4 and Jurkat T cells. While A20 overexpression is able to silence CBM complex-triggered NF-κB and MALT1 protease activation independent of ABIN-1, the negative regulatory function of ABIN-1 depends on A20. 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. Our 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 CBM complex from the negative impact of both regulators. Ubiquitin binding to A20 ZnF4/7 promotes destructive K48-polyubiquitination to itself and to ABIN-1. Further, after prolonged T cell stimulation, ABIN-1 antagonizes MALT1-catalyzed cleavage of re-synthesized A20 and thereby diminishes 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. © 2022, The Author(s). |
eng |
dc.language.iso |
eng |
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dc.publisher |
Cham (ZG) : Springer International Publishing AG |
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dc.relation.ispartofseries |
Cellular and molecular life sciences : (CMLS) 79 (2022), Nr. 2 |
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dc.rights |
CC BY 4.0 Unported |
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dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
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dc.subject |
CARMA1 |
eng |
dc.subject |
Immune activation |
eng |
dc.subject |
Immune suppression |
eng |
dc.subject |
T cell signaling |
eng |
dc.subject |
TNFAIP3 |
eng |
dc.subject |
TNIP1 |
eng |
dc.subject.ddc |
570 | Biowissenschaften, Biologie
|
ger |
dc.subject.ddc |
610 | Medizin, Gesundheit
|
ger |
dc.title |
A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells |
eng |
dc.type |
Article |
|
dc.type |
Text |
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dc.relation.essn |
1420-9071 |
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dc.relation.doi |
https://doi.org/10.1007/s00018-022-04154-z |
|
dc.bibliographicCitation.issue |
2 |
|
dc.bibliographicCitation.volume |
79 |
|
dc.bibliographicCitation.firstPage |
112 |
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dc.description.version |
publishedVersion |
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tib.accessRights |
frei zug�nglich |
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