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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.

Pubmed ID: 10531362


  • Hanai J
  • Chen LF
  • Kanno T
  • Ohtani-Fujita N
  • Kim WY
  • Guo WH
  • Imamura T
  • Ishidou Y
  • Fukuchi M
  • Shi MJ
  • Stavnezer J
  • Kawabata M
  • Miyazono K
  • Ito Y


The Journal of biological chemistry

Publication Data

October 29, 1999

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI23283

Mesh Terms

  • Activin Receptors, Type I
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Germ Cells
  • Immunoglobulins
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Receptors, Transforming Growth Factor beta
  • Signal Transduction
  • Smad3 Protein
  • Trans-Activators
  • Transcription Factor AP-2
  • Transcription Factors
  • Transcriptional Activation
  • Transforming Growth Factor beta