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Mol. Biol. Cell 14 (3): 1158-1171

Copyright © 2003 by The American Society for Cell Biology.

Vol. 14, Issue 3, 1158-1171, March 2003

Hic-5 Communicates between Focal Adhesions and the Nucleus through Oxidant-Sensitive Nuclear Export Signal

Motoko Shibanuma,dagger Joo-ri Kim-Kaneyama, Keiko Ishino, Nobuko Sakamoto, Tomoko Hishiki, Kaeko Yamaguchi, Kazunori Mori, Jun-ichi Mashimo, and Kiyoshi Nose

Department of Microbiology, Showa University School of Pharmaceutical Sciences, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, Japan

hic-5 was originally isolated as an H2O2-inducible cDNA clone whose product was normally found at focal adhesions. In this study, we found that Hic-5 accumulated in the nucleus in response to oxidants such as H2O2. Other focal adhesion proteins including paxillin, the most homologous to Hic-5, remained in the cytoplasm. Mutation analyses revealed that the C- and N-terminal halves of Hic-5 contributed to its nuclear localization in a positive and negative manner, respectively. After the finding that leptomycin B (LMB), an inhibitor of nuclear export signal (NES), caused Hic-5 to be retained in the nucleus, Hic-5 was demonstrated to harbor NES in the N-terminal, which was sensitive to oxidants, thereby regulating the nuclear accumulation of Hic-5. NES consisted of a leucine-rich stretch and two cysteines with a limited similarity to Yap/Pap-type NES. In the nucleus, Hic-5 was suggested to participate in the gene expression of c-fos. Using dominant negative mutants, we found that Hic-5 was actually involved in endogenous c-fos gene expression upon H2O2 treatment. Hic-5 was thus proposed as a focal adhesion protein with the novel aspect of shuttling between focal adhesions and the nucleus through an oxidant-sensitive NES, mediating the redox signaling directly to the nucleus.


dagger Corresponding author. E-mail address: smotoko{at}pharm.showa-u.ac.jp.


Molecular Biology of the Cell
Vol. 14, 1158-1171, March 2003
Copyright © 2003 by The American Society for Cell Biology


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