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

Mol. Biol. Cell, 1 March 2003
Vol. 14, Issue 3, p. 1158-1171
DOI: 10.1091/mbc.02-06-0099

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

  1. Motoko Shibanuma,
  2. Joo-ri Kim-Kaneyama,
  3. Keiko Ishino,
  4. Nobuko Sakamoto,
  5. Tomoko Hishiki,
  6. Kaeko Yamaguchi,
  7. Kazunori Mori,
  8. Jun-ichi Mashimo, and
  9. Kiyoshi Nose
  1. 1 Department of Microbiology, Showa University School of Pharmaceutical Sciences, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, Japan
  1. Keith R. Yamamoto, Monitoring Editor
  • Submitted June 13, 2002.
  • Revised October 30, 2002.
  • Accepted November 25, 2002.


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.



M. Shibanuma, J.-r. Kim-Kaneyama, K. Ishino, N. Sakamoto, T. Hishiki, K. Yamaguchi, K. Mori, J.-i. Mashimo, K. Nose, and K. R. Yamamoto, Hic-5 Communicates between Focal Adhesions and the Nucleus through Oxidant-Sensitive Nuclear Export Signal. Mol. Biol. Cell 14, 1158-1171 (2003).

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