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Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):335-47.

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

Author information

1
Department of Microbiology, Showa University School of Pharmaceutical Sciences, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8555, Japan. smotoko@pharm.showa-u.ac.jp

Abstract

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.

PMID:
15706082
DOI:
10.1089/ars.2005.7.335
[Indexed for MEDLINE]

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