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J Biol Chem, Vol. 274, Issue 44, 31577-31582, October 29, 1999
PROMOTER
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From the Smads are signal transducers for members of the
transforming growth factor- Department of Biochemistry, The Cancer
Institute of the Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 70-8455, Japan, the ¶ Department
of Viral Oncology, Institute for Virus Research, Kyoto University,
Shogo-in, Sakyo-ku, Kyoto 606-8507, Japan, and the Department of
Molecular Genetics and Microbiology, Graduate Program in Immunology and
Virology, University of Massachusetts Medical School, Worcester,
Massachusetts 01655-0122
(TGF-) 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 and subunits. The subunits of PEBP2/CBF, which contain the highly
conserved Runt domain, play essential roles in hematopoiesis and
osteogenesis. Here we show that three mammalian subunits of
PEBP2/CBF form complexes with R-Smads that act in TGF-/activin
pathways as well as those acting in bone morphogenetic protein (BMP)
pathways. Among them, PEBP2C/CBFA3/AML2 forms a complex with Smad3
and stimulates transcription of the germline Ig C 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-/BMP signaling.
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