title: Differential effects of the Ski-interacting protein (SKIP) on differentiation induced by transforming growth factor-beta1 and bone morphogenetic protein-2 in C2C12 cells.
abstract: The transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMP) are key regulatory factors that affect many critical cellular events in growth and development. Recently, we have shown that the Ski-interacting protein (SKIP) can augment TGF-beta signals. Here, we extended these studies by examining the biologic consequences of SKIP overexpression on TGF-beta1 and BMP-2 signals in C2C12 cells. C2C12 myoblasts differentiate into myotubes when the media is depleted of mitogenic factors, and TGF-beta1 inhibits this myotube formation. BMP-2 not only inhibits the myotube formation, but also induces C2C12 cells to differentiate into osteoblasts. Here, we show that SKIP-overexpressing C2C12 cells treated with TGF-beta1 or BMP-2 displayed no differences in comparison to vector control cells in their ability to form myotubes or in the expression of the myogenic markers myosin heavy chain-1 and myogenin. Unexpectedly, SKIP-overexpressing C2C12 cells treated with BMP-2 displayed suppressed expression of the induced osteoblast markers alkaline phosphatase, osteocalcin, and the transcription factor Runx2. Lastly, SKIP could repress transcription induced by BMP-2 in luciferase reporter assays done in C2C12 cells. These data show that SKIP has specific inhibitory effects on BMP-2-induced differentiation and implicate SKIP to be a novel regulator of the differentiation programming induced by TGF-beta signals.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794-5222, USA.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hayman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D051379:Mice; D032342:Muscle Cells / Q000166:cytology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009687:Nuclear Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: D015415:Biomarkers; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D009687:Nuclear Proteins; C491762:Skiip protein, mouse; C508961:Tgfb1 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1