Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34. - Archive ouverte HAL Access content directly
Journal Articles Cell Communication and Signaling Year : 2013

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

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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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inserm-00821397 , version 1 (09-05-2013)

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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, 2013, 11 (1), pp.25. ⟨10.1186/1478-811X-11-25⟩. ⟨inserm-00821397⟩
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