B-ind1, a novel mediator of Rac1 signaling cloned from sodium butyrate-treated fibroblasts

Sodium butyrate is a multifunctional agent known to inhibit cell proliferat ion and to induce differentiation by modulating transcription. We have perf ormed differential display analysis to identify transcriptional targets of sodium butyrate in Balb/c BP-A31 mouse fibroblasts. A novel butyrate-induce d transcript B-ind1 has been cloned by this approach. The human homologue o f this transcript contains an open reading frame that codes for a protein o f 370 amino acids without known functional motifs, In transfected cells, th e B-ind1 protein has been found to potentiate different effects of the smal l GTPase Rad, such as c-Jun N-terminal kinase activation and transcriptiona l activity of nuclear factor kappa B (NF-kappa B), In addition, we have dem onstrated that B-ind1 forms complexes with the constitutively activated Rad protein, To investigate the role of B-ind1 in Rad signaling, we have const ructed several deletion mutants of B-ind1 and tested their ability to affec t the activation of NF-kappa B by Rad. Interestingly, the fragment encoding the median region of human B-ind1 acted as a dominant-negative variant to block Rad-mediated NF-kappa B activity. These data define B-ind1 as a novel component of Rac1-signaling pathways leading to the modulation of gene exp ression.