Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.

Konstantinos Poalas; Emeline Hatchi; Nelia Cordeiro; Sonia Dubois; Héloïse Leclair; Claire Leveau; Catherine Alexia; Julie Gavard; Aimé Vazquez; Nicolas Bidère

doi:10.1186/1478-811X-11-25

Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.

Konstantinos Poalas ¹ Emeline Hatchi ¹ Nelia Cordeiro ¹ Sonia Dubois ¹ Héloïse Leclair ² Claire Leveau ¹ Catherine Alexia ¹ Julie Gavard ² Aimé Vazquez ¹ Nicolas Bidère ^{1, *}

* Auteur correspondant

1 Régulation de la survie cellulaire et des allogreffes

2 UM3 (UMR 8104 / U1016) - Institut Cochin

Abstract : BACKGROUND: NF-κB is a master gene regulator involved in plethora of biological processes, including lymphocyte activation and proliferation. Reversible ubiquitinylation of key adaptors is required to convey the optimal activation of NF-κB. However the deubiquitinylases (DUBs), which catalyze the removal of these post-translational modifications and participate to reset the system to basal level following T-Cell receptor (TCR) engagement continue to be elucidated. FINDINGS: Here, we performed an unbiased siRNA library screen targeting the DUBs encoded by the human genome to uncover new regulators of TCR-mediated NF-κB activation. We present evidence that knockdown of Ubiquitin-Specific Protease 34 (USP34) selectively enhanced NF-κB activation driven by TCR engagement, similarly to siRNA against the well-characterized DUB cylindromatosis (CYLD). From a molecular standpoint, USP34 silencing spared upstream signaling but led to a more pronounced degradation of the NF-κB inhibitor IκBα, and culminated with an increased DNA binding activity of the transcription factor. CONCLUSIONS: Collectively, our data unveils USP34 as a new player involved in the fine-tuning of NF-κB upon TCR stimulation.

Mots-clés : DUBs NF-κB Ubiquitinylation T-Cell receptor

Type de document :

Article dans une revue

Cell Communication and Signaling, BioMed Central, 2013, 11 (1), pp.25. 〈10.1186/1478-811X-11-25〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire / Biochimie [q-bio.BM]

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00821397
Contributeur : Ed. Bmc <>
Soumis le : jeudi 9 mai 2013 - 21:09:12
Dernière modification le : jeudi 11 janvier 2018 - 06:23:10
Document(s) archivé(s) le : samedi 10 août 2013 - 04:12:32

Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.

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Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.

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