Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2007-09-06Keywords
Active Transport, Cell NucleusAnimals
Bone Morphogenetic Proteins
Cell Nucleus
DNA-Binding Proteins
Drosophila
Drosophila Proteins
Genome, Insect
Humans
Karyopherins
RNA Interference
Receptors, Cytoplasmic and Nuclear
Smad Proteins
Transcription Factors
Transforming Growth Factor beta
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Cell Biol. 2007 Sep 10;178(6):981-94. Epub 2007 Sep 4. Link to article on publisher's siteDOI
10.1083/jcb.200703106Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38413PubMed ID
17785517Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1083/jcb.200703106