Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter
Department of Molecular Genetics and Microbiology
*Activin Receptors, Type I; Bone Morphogenetic Proteins; DNA-Binding Proteins; Germ Cells; Immunoglobulins; Promoter Regions (Genetics); Protein Binding; Protein-Serine-Threonine Kinases; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad3 Protein; *Trans-Activation (Genetics); Trans-Activators; Transcription Factor AP-2; Transcription Factors; Transforming Growth Factor beta
Life Sciences | Medicine and Health Sciences | Women's Studies
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.
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Citation: J Biol Chem. 1999 Oct 29;274(44):31577-82.