TY - JOUR T1 - Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads. JF - J Cell Biol Y1 - 2007 A1 - Xu, Lan A1 - Yao, Xiaohao A1 - Chen, Xiaochu A1 - Lu, Peiyuan A1 - Zhang, Biliang A1 - Ip, Y Tony KW - Active Transport, Cell Nucleus KW - Animals KW - Bone Morphogenetic Protein 2 KW - Bone Morphogenetic Proteins KW - Cell Nucleus KW - DNA-Binding Proteins KW - Drosophila KW - Drosophila Proteins KW - Genome, Insect KW - Humans KW - Karyopherins KW - Receptors, Cytoplasmic and Nuclear KW - RNA Interference KW - Smad Proteins KW - Transcription Factors KW - Transforming Growth Factor beta AB -

Nuclear translocation of Smad proteins is a critical step in signal transduction of transforming growth factor beta (TGF-beta) and bone morphogenetic proteins (BMPs). Using nuclear accumulation of the Drosophila Smad Mothers against Decapentaplegic (Mad) as the readout, we carried out a whole-genome RNAi screening in Drosophila cells. The screen identified moleskin (msk) as important for the nuclear import of phosphorylated Mad. Genetic evidence in the developing eye imaginal discs also demonstrates the critical functions of msk in regulating phospho-Mad. Moreover, knockdown of importin 7 and 8 (Imp7 and 8), the mammalian orthologues of Msk, markedly impaired nuclear accumulation of Smad1 in response to BMP2 and of Smad2/3 in response to TGF-beta. Biochemical studies further suggest that Smads are novel nuclear import substrates of Imp7 and 8. We have thus identified new evolutionarily conserved proteins that are important in the signal transduction of TGF-beta and BMP into the nucleus.

VL - 178 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/17785517?dopt=Abstract ER -