title: 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.
  
  
  RESULTS
  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.
authors.affiliation: INSERM UMR_S 1014, Hôpital Paul Brousse, Villejuif 94800, France. nicolas.bidere@inserm.fr.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poalas
authors.forename: Emeline M
authors.initials: EM
authors.lastname: Hatchi
authors.forename: Nelia
authors.initials: N
authors.lastname: Cordeiro
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Dubois
authors.forename: Héloïse M
authors.initials: HM
authors.lastname: Leclair
authors.forename: Claire
authors.initials: C
authors.lastname: Leveau
authors.forename: Catherine
authors.initials: C
authors.lastname: Alexia
authors.forename: Julie
authors.initials: J
authors.lastname: Gavard
authors.forename: Aimé
authors.initials: A
authors.lastname: Vazquez
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bidère