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J. Biol. Chem., Vol. 283, Issue 33, 22867-22874, August 15, 2008
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From the Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605
Trafficking of Smad proteins between the cytoplasm and nucleus is a critical component of transforming growth factor β (TGF-β) signal transduction. Smad4 translocates into the nucleus either in response to TGF-β stimulation or when its nuclear export is blocked by leptomycin B (LMB). We demonstrate that both TGF-β-induced and basal state spontaneous nuclear import of Smad4 require importin 7 and 8 (Imp7,8). Our data suggest that in the nuclear import of Smad4, the role of Imp8 is irreplaceable by Imp7, and that Smads preferentially bind Imp8. Interestingly, in contrast to its mammalian counterpart Smad4, Drosophila Medea appears to utilize different mechanisms for TGF-β-induced or basal state nuclear accumulation, with the latter independent of Msk (Drosophila Imp7/8) function. In addition, overexpression of Imp8 alone was sufficient to cause an increased concentration of Smad1, 3 and 4 in the nucleus, but had very limited effects on Smad2. These observations suggest selective involvement of Imp8/Msk in nuclear import of different Smads under different conditions.
Received for publication, February 19, 2008 , and in revised form, May 30, 2008.
* This work was supported, in whole or in part, by National Institutes of Health Grant R01CA108509. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and Tables S1-S5.
1 To whom correspondence should be addressed: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Rm. 308, Worcester, MA 01605. Tel.: 508-856-4273; Fax: 508-856-6662; E-mail: lan.xu{at}umassmed.edu.
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