J. Hanai et al., Interaction and functional cooperation of PEBP2/CBF with Smads - Synergistic induction of the immunoglobulin germline C alpha promoter, J BIOL CHEM, 274(44), 1999, pp. 31577-31582
Smads are signal transducers for members of the transforming growth factor-
beta (TGF-beta) superfamily. Upon ligand stimulation, receptor-regulated Sm
ads (R-Smads) are phosphorylated by serine/threonine kinase receptors, form
complexes with common-partner Smad, and translocate into the nucleus, wher
e they regulate the transcription of target genes together with other trans
cription factors. Polyomavirus enhancer binding protein 2/core binding fact
or (PEEP2/CBF) is a transcription factor complex composed of alpha and beta
subunits. The alpha subunits of PEEP2/CBF, which contain the highly conser
ved Hunt domain, play essential roles in hematopoiesis and osteogenesis. He
re we show that three mammalian alpha subunits of PEBP2/CEF 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/CBF
A3/AML2 forms a complex with Smads and stimulates transcription of the germ
line Ig C alpha promoter in a cooperative manner, for which binding of both
factors to their specific binding sites is essential. PEEPS may thus be a
nuclear target of TGF-beta/BMP signaling.