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Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.

The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vitro association and pull-down experiments, we demonstrate that Gro and its mammalian homolog TLE1 specifically interact with AML1 and AML2. In addition to the VWRPY motif, other C-terminal sequences are required for these interactions with Gro/TLE1. TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells. LEF-1 is an additional transcription factor that mediates transactivation of TCR enhancers. LEF-1 and its Drosophila homolog Pangolin (Pan) are involved in the Wnt/Wg signaling pathway through interactions with the coactivator beta-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:beta-catenin-dependent transcription. These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling.

Pubmed ID: 9751710


  • Levanon D
  • Goldstein RE
  • Bernstein Y
  • Tang H
  • Goldenberg D
  • Stifani S
  • Paroush Z
  • Groner Y


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 29, 1998

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Armadillo Domain Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Cell Line
  • Core Binding Factor Alpha 2 Subunit
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Drosophila
  • Drosophila Proteins
  • Genes, Reporter
  • Humans
  • Insect Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Neoplasm Proteins
  • Nuclear Proteins
  • Protein Binding
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae
  • Trans-Activators
  • Transcription Factors
  • Transfection
  • beta Catenin