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Biomedical subjects

Kiyoshi Nose

Publications and source records attributed to Kiyoshi Nose.

22 records · Page 2Linked to original sources

[Regulation of gene expression by active oxygen species].

Reactive oxygen species (ROS) are generated from cells stimulated by various cytokines, hormones, and stresses, and regulate cellular functions such as gene expression and cell growth. They affect activities of many types of molecular targets, including signaling molecules and transcription factors. Early-response genes (c-fos, egr-I and JE) that encode transcription factors are induced by ROS, and activities of their products are modulated by ROS through redox-based mechanisms. We isolated a novel gene, hic-5, that was induced by hydrogen peroxide and encodes a focal adhesion protein. hic-5 was found to translocate to the nucleus in cells treated with ROS and regulates several cellular genes. We propose that hic-5 is a key element in the transduction of signals from the cell surface to the nucleus under oxidative stress.

Animals↗

Involvement of FAK and PTP-PEST in the regulation of redox-sensitive nuclear-cytoplasmic shuttling of a LIM protein, Hic-5.

The LIM protein Hic-5 is a focal adhesion protein shuttling in and out of the nucleus through the redox-sensitive nuclear export signal, and unlike other focal adhesion proteins including paxillin, the protein most homologous to Hic-5, it accumulates in the nucleus under oxidative conditions and participates in the transcription of c-fos and p21(Cip1) genes. Here, we examined the roles of the interacting partners of Hic-5, focal adhesion kinase (FAK) and protein tyrosine phosphatase PEST (PTP-PEST), in the nuclear translocation of Hic-5 and found that they were inhibitory. Interestingly, the interaction of Hic-5 with FAK was regulated by specific cysteines near the binding site and decreased in cells under oxidative conditions. Its interaction with PTP-PEST was also sensitive to the oxidant. These results suggest that the nuclear-cytoplasmic shuttling of Hic-5 is regulated by its interacting partners at focal adhesions or in the cytoplasm in a redox-sensitive manner, coordinating its role at focal adhesions with that in the nucleus, depending on the redox state of cells. Cytochalasin D or a phorbol ester also induced nuclear accumulation of Hic-5, which was inhibited by scavengers of reactive oxygen species (ROS), suggesting that besides oxidants, endogenously produced ROS induced the nuclear accumulation of Hic-5.

Active Transport, Cell Nucleus↗