Negative regulation of NF-κB signaling in T lymphocytes by the ubiquitin-specific protease USP34.
Résumé
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.
Fichier principal
1478-811X-11-25.pdf (467.78 Ko)
Télécharger le fichier
1478-811X-11-25-S1.PDF (98.01 Ko)
Télécharger le fichier
1478-811X-11-25-S2.PDF (68.54 Ko)
Télécharger le fichier
1478-811X-11-25-S3.TIFF (1.58 Mo)
Télécharger le fichier
1478-811X-11-25-S4.TIFF (668.12 Ko)
Télécharger le fichier
1478-811X-11-25.xml (37.82 Ko)
Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Format : Autre
Format : Autre
Format : Autre
Format : Autre
Format : Autre