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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.

Accumulation of Focal Adhesion Protein Hic-5 in the Nucleus by Hydrogen Peroxide.