Preferential utilization of Imp7/8 in nuclear import of Smads

Student Author(s)

Charisa Cottonham; Xiaochu Chen

Academic Program

Interdisciplinary Graduate Program

UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Life Sciences | Medicine and Health Sciences


Trafficking of Smad proteins between the cytoplasm and nucleus is a critical component of transforming growth factor beta (TGF-beta) signal transduction. Smad4 translocates into the nucleus either in response to TGF-beta stimulation or when its nuclear export is blocked by leptomycin B (LMB). We demonstrate that both TGF-beta-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-beta-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.

DOI of Published Version



J Biol Chem. 2008 Aug 15;283(33):22867-74. Epub 2008 Jun 2. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID