Accumulation of focal adhesion protein hic-5 in the nucleus by hydrogen peroxide

Reactive oxygen species (ROS) are produced in cultured cells upon stimulation with cytokines and tumor promoters, and participate in signal transduction pathways leading to gene expression. The hic-5 gene was isolated as a hydrogen peroxide-inducible clone by differential screening, and was shown to encode a paxillin-related protein localized in the focal adhesion plaques. In mouse osteoblastic and fibroblastic cells treated with low concentrations of hydrogen peroxide, Hic-5 protein was found to be reversibly localized to the nucleus within 30 min. Hic-5 was also translocated to the nucleus in cells treated with leptomycin B, an inhibitor of nuclear export of proteins. Hic-5 protein with mutations in the nuclear export signal and the LIM-3 domain accumulated in the nucleus. These results indicated that Hic-5 shuttles between the cytoplasm and the nucleus, and may participate both in surface signals and in gene expression.