title: Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor.
abstract: Inactivation of bone morphogenetic protein signaling via mutation of the BMPR-IA TGF-beta superfamily type I receptor causes familial juvenile polyposis, an inherited gastrointestinal cancer predisposition syndrome. In an effort to provide new insight into the mechanism(s) of BMP-mediated tumor suppression, we employed a yeast two-hybrid screen to identify novel proteins that interact with the intracellular domain of BMPR-IA. 30/31 interacting clones encoded SAP49, a splicing factor that has been shown to be required for normal development in Caenorhabditis elegans. The remaining interacting clone was FKBP12.6, a known TGF-beta type I receptor interactor. The interaction between BMPR-IA and SAP49 was confirmed via coimmunoprecipitation in human cells. Mutational analysis demonstrated that the GS domain of the receptor and the conserved proline-rich domain of SAP49 were required for the interaction. Co-localization studies suggested that the interaction may occur at the inner leaflet of the nuclear membrane. These data suggest that BMPR-IA may interact with and modulate the activity of a developmentally relevant splicing factor.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA.
authors.forename: Tagvor G
authors.initials: TG
authors.lastname: Nishanian
authors.forename: Todd
authors.initials: T
authors.lastname: Waldman
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D052005:Bone Morphogenetic Protein Receptors, Type I; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D018398:Homeodomain Proteins; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017978:Receptors, Growth Factor; C486347:SF3B4 protein, human; D016212:Transforming Growth Factor beta; D011392:Proline; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I