Details

Autor(en) / Beteiligte

• Shibanuma, Motoko
• Mori, Kazunori
• Kim-Kaneyama, Joo-Ri
• Nose, Kiyoshi

Titel

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

Ist Teil von

• Antioxidants & redox signaling, 2005-03, Vol.7 (3-4), p.335-347

Ort / Verlag

United States

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.