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J. Cell Biol. 165 (5): 617-623

Copyright © 2004 by the Rockefeller University Press.


Cellular stresses induce the nuclear accumulation of importin {alpha} and cause a conventional nuclear import block

Yoichi Miyamoto1, Takuya Saiwaki1, Junichi Yamashita1, Yoshinari Yasuda1, Ippei Kotera1, Satoshi Shibata1, Masaki Shigeta2, Yasushi Hiraoka2,3,4, Tokuko Haraguchi2,3,4, , and Yoshihiro Yoneda1

1 Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
2 Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan
3 Core Research for Evolutional Science and Technology of Japan Science and Technology, National Institute for Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan
4 Kansai Advanced Research Center, National Institute for Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan

Address correspondence to Y. Yoneda, Dept. of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-4605. Fax: 81-6-6879-4609. email: yyoneda{at}; or T. Haraguchi, email: tokuko{at}

Abstract: We report here that importin {alpha} accumulates reversibly in the nucleus in response to cellular stresses including UV irradiation, oxidative stress, and heat shock. The nuclear accumulation of importin {alpha} appears to be triggered by a collapse in the Ran gradient, resulting in the suppression of the nuclear export of importin {alpha}. In addition, nuclear retention and the importin ß/Ran-independent import of importin {alpha} also facilitate its rapid nuclear accumulation. The findings herein show that the classical nuclear import pathway is down-regulated via the removal of importin {alpha} from the cytoplasm in response to stress. Moreover, whereas the nuclear accumulation of heat shock cognate 70 is more sensitive to heat shock than the other stresses, importin {alpha} is able to accumulate in the nucleus at all the stress conditions tested. These findings suggest that the stress-induced nuclear accumulation of importin {alpha} can be involved in a common physiological response to various stress conditions.

Key Words: cellular stress; importin/karyopherin; nuclear transport; nuclear localization signal; Ran

The online version of this article includes supplemental material.

Abbreviation used in this paper: hsc, heat shock cognate.

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