Bcl3, an I kappa B protein, stimulates activating protein-1 transactivation and cellular proliferation

Bcl3, an I kappa B protein, was originally isolated as a putative proto-onc ogene in a subset of B cell chronic lymphocytic leukemias. Bcl3 was subsequ ently shown to associate tightly with and transactivate the NF kappa B p50 or p52 homodimer. Herein, we show that Bcl3 stimulates the activating prote in-1 (AP-1) transactivation, either alone or in conjunction with transcript ion integrators steroid receptor coactivator-l and CREB-binding protein/p30 0. The C-terminal 158 residues of Bcl3 exhibited an autonomous transactivat ion function and interacted with specific subregions of the AP-1 components c-Jun and c-Fos, CREB-binding protein/p300, and steroid receptor coactivat or-l, as demonstrated by the yeast and mammalian two-hybrid tests as well a s glutathione S-transferase pull-down assays. In addition, anti-HA antibody co-precipitated c-Jun from HeLa cells co-expressing c-Jun and HA-tagged Bc l3, consistent with the idea that Bcl3 directly associates with AP-1 in viv o. Furthermore, microinjection of Bcl3 expression vector into Rat-1 fibrobl ast cells significantly enhanced DNA synthesis and expression of c-jun, one of the cellular target genes of AP-1. These results suggest that Bcl3 may directly participate in the tumorigenesis processes as a novel transcriptio n coactivator of the mitogenic transcription factor AP-1 in vivo.