Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha 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, 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.
Hanai
J
J
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 70-8455, Japan.
Chen
L F
LF
Kanno
T
T
Ohtani-Fujita
N
N
Kim
W Y
WY
Guo
W H
WH
Imamura
T
T
Ishidou
Y
Y
Fukuchi
M
M
Shi
M J
MJ
Stavnezer
J
J
Kawabata
M
M
Miyazono
K
K
Ito
Y
Y
D030201:Activin Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005854:Germ Cells; D007136:Immunoglobulins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein; D015534:Trans-Activators / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I