To gain insights on how PALS1 modulate NF-kB, we first investigated the transcription factor binding ability by electrophoretic mobility shift assay (EMSA). Less NF-kB bound to its specific probe in nuclei extracts from PALS1-siRNA transfected cells following TCR stimulation ( Figure 4A ). As expected, Oct-1 binding remained unchanged without PALS1. Consistent with a diminished NF-kB activity, both the phosphorylation and subsequent proteasomal degradation of NF-kB inhibitor, IkBa, were severely decreased in the absence of PALS1 ( Figure 4B ). Because TCR-induced NF-kB activation relies on the assembly of the CBM complex [15] , BCL10 was immunoprecipitated from nonspecific (NS-) and PALS1-siRNA transfected Jurkat cells. MALT1, which forms an heterodimer with BCL10, coprecipitated with BCL10 regardless of stimulation. Although PALS1 was not found bound to BCL10, its absence diminished CARMA1 recruitment ( Figure 4C , and data not shown). Hence, our data suggest that PALS1 participates to the optimal translocation and activation of NF-kB upon TCR stimulation, possibly by favoring the CBM assembly.