A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Hongli Yin
  • Ozge Karayel
  • Ying Yin Chao
  • Thomas Seeholzer
  • Isabel Hamp
  • Oliver Plettenburg
  • Torben Gehring
  • Christina Zielinski
  • Matthias Mann
  • Daniel Krappmann

Externe Organisationen

  • Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
  • Max-Planck-Institut für Biochemie
  • Friedrich-Schiller-Universität Jena
  • Technische Universität München (TUM)
  • Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V.Hans-Knöll-Institut
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Details

OriginalspracheEnglisch
Aufsatznummer112
FachzeitschriftCellular and Molecular Life Sciences
Jahrgang79
Ausgabenummer2
Frühes Online-Datum31 Jan. 2022
PublikationsstatusVeröffentlicht - Feb. 2022

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.

ASJC Scopus Sachgebiete

Zitieren

A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. / Yin, Hongli; Karayel, Ozge; Chao, Ying Yin et al.
in: Cellular and Molecular Life Sciences, Jahrgang 79, Nr. 2, 112, 02.2022.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Yin, H, Karayel, O, Chao, YY, Seeholzer, T, Hamp, I, Plettenburg, O, Gehring, T, Zielinski, C, Mann, M & Krappmann, D 2022, 'A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells', Cellular and Molecular Life Sciences, Jg. 79, Nr. 2, 112. https://doi.org/10.1007/s00018-022-04154-z
Yin, H., Karayel, O., Chao, Y. Y., Seeholzer, T., Hamp, I., Plettenburg, O., Gehring, T., Zielinski, C., Mann, M., & Krappmann, D. (2022). A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. Cellular and Molecular Life Sciences, 79(2), Artikel 112. https://doi.org/10.1007/s00018-022-04154-z
Yin H, Karayel O, Chao YY, Seeholzer T, Hamp I, Plettenburg O et al. A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. Cellular and Molecular Life Sciences. 2022 Feb;79(2):112. Epub 2022 Jan 31. doi: 10.1007/s00018-022-04154-z
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title = "A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells",
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.",
keywords = "CARMA1, Immune activation, Immune suppression, T cell signaling, TNFAIP3, TNIP1",
author = "Hongli Yin and Ozge Karayel and Chao, {Ying Yin} and Thomas Seeholzer and Isabel Hamp and Oliver Plettenburg and Torben Gehring and Christina Zielinski and Matthias Mann and Daniel Krappmann",
note = "Funding Information: Open Access funding enabled and organized by Projekt DEAL. Work of D.K. was supported by the Deutsche Forschungsgemeinschaft SFB1054 (A04, ID210592381) and SFB1335 (P07, ID360372040). Work of CZ was supported by the Deutsche Forschungsgemeinschaft SFB1054 (B10, ID210592381), SFB1335 (P18, ID360372040), Collaborative Research Centre (CRC)/Transregio124 FungiNet (C7, No 210879364) and the Carl-Zeiss-Stiftung. ",
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Download

TY - JOUR

T1 - A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells

AU - Yin, Hongli

AU - Karayel, Ozge

AU - Chao, Ying Yin

AU - Seeholzer, Thomas

AU - Hamp, Isabel

AU - Plettenburg, Oliver

AU - Gehring, Torben

AU - Zielinski, Christina

AU - Mann, Matthias

AU - Krappmann, Daniel

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. Work of D.K. was supported by the Deutsche Forschungsgemeinschaft SFB1054 (A04, ID210592381) and SFB1335 (P07, ID360372040). Work of CZ was supported by the Deutsche Forschungsgemeinschaft SFB1054 (B10, ID210592381), SFB1335 (P18, ID360372040), Collaborative Research Centre (CRC)/Transregio124 FungiNet (C7, No 210879364) and the Carl-Zeiss-Stiftung.

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

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KW - Immune activation

KW - Immune suppression

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KW - TNIP1

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