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Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter.

http://www.ncbi.nlm.nih.gov/pubmed/10531362

Smads are signal transducers for members of the transforming growth factor-beta (TGF-beta) superfamily. Upon ligand stimulation, receptor-regulated Smads (R-Smads) are phosphorylated by serine/threonine kinase receptors, form complexes with common-partner Smad, and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors. Polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is a transcription factor complex composed of alpha and beta subunits. The alpha subunits of PEBP2/CBF, which contain the highly conserved Runt domain, play essential roles in hematopoiesis and osteogenesis. Here we show that three mammalian alpha subunits of PEBP2/CBF form complexes with R-Smads that act in TGF-beta/activin pathways as well as those acting in bone morphogenetic protein (BMP) pathways. Among them, PEBP2alphaC/CBFA3/AML2 forms a complex with Smad3 and stimulates transcription of the germline Ig Calpha promoter in a cooperative manner, for which binding of both factors to their specific binding sites is essential. PEBP2 may thus be a nuclear target of TGF-beta/BMP signaling.

Pubmed ID: 10531362 RIS Download

Mesh terms: Activin Receptors, Type I | Bone Morphogenetic Proteins | DNA-Binding Proteins | Germ Cells | Immunoglobulins | Promoter Regions, Genetic | Protein Binding | Protein-Serine-Threonine Kinases | Receptors, Transforming Growth Factor beta | Signal Transduction | Smad3 Protein | Trans-Activators | Transcription Factor AP-2 | Transcription Factors | Transcriptional Activation | Transforming Growth Factor beta

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Associated grants

  • Agency: NIAID NIH HHS, Id: R01 AI23283

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