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

Reactive oxygen species (ROS) are produced in cultured cells upon stimulati on with cytokines and tumor promoters, and participate in signal transducti on pathways leading to gene expression. The hic-5 gene was isolated as a hy drogen 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 concentratio ns 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 i n cells treated with leptomycin B, an inhibitor of nuclear export of protei ns. 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 shut tles between the cytoplasm and the nucleus, and may participate both in sur face signals and in gene expression.