Transcriptional activation of the c-fos gene by a LIM protein, Hic-5.

Hic-5 is a member of LIM family proteins with a striking similarity to paxillin and localizes primarily in the focal adhesion. We recently reported that Hic-5 translocated to the nucleus under oxidative stress and was involved in transcriptional regulation. In the present study, we extended these findings to show that transcription of c-fos gene was up-regulated by overexpression of Hic-5. In clonal stable transformants established from human immortalized fibroblasts by transfection of an expression vector of Hic-5, the constitutive level of c-fos mRNA was well correlated with that of Hic-5. In reporter assays using the luciferase gene under control of the human c-fos 5(')-upstream region from -2.2kb to +1, expression of Hic-5, that was engineered to accumulate in the nucleus, stimulated the transcriptional activity of the c-fos enhancer. From experiments using various deletions and point mutations, it was revealed that multiple sequences including GC/Sp1, Ets, and ERE/AP-1 elements found around the -1.3kb region were responsible for the activation by Hic-5. Hic-5 itself did not bind to these elements in a sequence specific manner, but p300 appeared to be involved in the induction of c-fos. These results suggest that Hic-5 participates in the transcriptional regulation of c-fos as a scaffold in transcriptional complexes.