The Kruppel-like transcriptional factors Zf9 and GKLF coactivate the humankeratin 4 promoter and physically interact

Zf9/CPBP/KLF6 is a widely expressed member of the Kruppel-like family of tr anscriptional factors which regulates gene expression in hepatic stellate c ells. Because of its ubiquitous expression including in the esophagus, we h ave explored its function in the esophageal squamous epithelium, a model sy stem to study cellular proliferation and differentiation. Reverse transcrip tion-PCR (RT-PCR) and Western blot analyses revealed that Zf9 was highly ex pressed in human esophageal squamous canter cell lines. Additionally, Zf9 l ocalizes to the esophageal squamous epithelium by immunohistochemistry. Usi ng transient transfection, Zf9 transactivates the human keratin 4 (K4) prom oter reporter gene construct in a subset of the esophageal cancer cell line s through indirect mechanisms. Co-transfection of Zf9 and GKLF/KLF4, which is also a member of the Kruppel-like factors and expressed in the esophagea l squamous epithelium, leads to coactivation in an additive fashion. Furthe rmore, we demonstrate that there is a physical interaction between GKLF and Zf9, a novel finding for Kruppel-like family members. (C) 2000 Federation of European Biochemical Societies.