Cellular stresses induce the nuclear accumulation of importin alpha and cause a conventional nuclear import block.
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 beta/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.
Miyamoto
Yoichi
Y
Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
Saiwaki
Takuya
T
Yamashita
Junichi
J
Yasuda
Yoshinari
Y
Kotera
Ippei
I
Shibata
Satoshi
S
Shigeta
Masaki
M
Hiraoka
Yasushi
Y
Haraguchi
Tokuko
T
Yoneda
Yoshihiro
Y
D021581:Active Transport, Cell Nucleus / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D028901:alpha Karyopherins; D020931:ran GTP-Binding Protein