Role of NFκB activator Act1 in CD40-mediated signaling in epithelial cells

CD40, a cell surface receptor in the tumor necrosis factor receptor family, first identified and functionally characterized on B lymphocytes, is also expressed on epithelial and other cells and is now thought to play a more general role in immune regulation. Overexpression of the NFkappaB activator 1 (Act1) leads to the activation of both NFkappaB and Jun kinase in epithelial cell lines. Enclogenous Act1 is recruited to the CD40 receptor in human intestinal (HT29) and cervical (HeLa) epithelial cells upon stimulation with CD40 ligand, indicating that Actl is involved in this signaling pathway. Actl also interacts with tumor necrosis factor receptor-associated factor 3, a component involved in CD40-activated pathway. Furthermore, transfection of Actl into C33A cervical epithelial cells, which do not express it, renders these cells sensitive to CD40 ligand-induced NFkappaB activation and protects them from CD40 ligand-induced apoptosis. We conclude that Act1 plays an important role in CD40-mediated signaling in epithelial cells.