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

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.
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Cell Communication and Signaling, BioMed Central, 2013, 11 (1), pp.25. 〈10.1186/1478-811X-11-25〉
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Soumis le : jeudi 9 mai 2013 - 21:09:12
Dernière modification le : jeudi 11 janvier 2018 - 06:23:10
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Konstantinos Poalas, Emeline Hatchi, Nelia Cordeiro, Sonia Dubois, Héloïse Leclair, et al.. Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.. Cell Communication and Signaling, BioMed Central, 2013, 11 (1), pp.25. 〈10.1186/1478-811X-11-25〉. 〈inserm-00821397〉

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