Interaction and Functional Cooperation of PEBP2/CBF with Smads: SYNERGISTIC INDUCTION OF THE IMMUNOGLOBULIN GERMLINE C alpha PROMOTER

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, PEBP2 alpha C/CBFA3/AML2 forms a complex with Smad3 and stimulates transcription of the germline Ig C alpha 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.