Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (20), p.11590-11595
1998
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- Autor(en) / Beteiligte
- Titel
- Transcriptional Repression by AML1 and LEF-1 Is Mediated by the TLE/Groucho Corepressors
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (20), p.11590-11595
- Ort / Verlag
- United States: National Academy of Sciences of the United States of America
- Erscheinungsjahr
- 1998
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mammalian AML/CBFα 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 α and β , 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 β -catenine and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:β -catenine-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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.95.20.11590Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_21685
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Armadillo Domain Proteins, Basic Helix-Loop-Helix Transcription Factors, beta Catenin, Binding Sites, Biochemistry, Biological Sciences, Cell Line, Co repressor proteins, Core Binding Factor Alpha 2 Subunit, Cytoskeletal Proteins - metabolism, DNA-Binding Proteins - chemistry, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Drosophila, Drosophila - genetics, Drosophila - metabolism, Drosophila Proteins, Genes, Genes, Reporter, Humans, Insect Proteins - genetics, Insect Proteins - metabolism, Lymphoid Enhancer-Binding Factor 1, Myeloid leukemia, Neoplasm Proteins, Nuclear Proteins - chemistry, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Plasmids, Protein Binding, Proteins, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, alpha-beta - genetics, Receptors, Antigen, T-Cell, alpha-beta - metabolism, Recombinant Fusion Proteins - chemistry, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - metabolism, Repressor Proteins - chemistry, Repressor Proteins - genetics, Repressor Proteins - metabolism, Saccharomyces cerevisiae - genetics, Saccharomyces cerevisiae - metabolism, T cell antigen receptors, T lymphocytes, Trans-Activators, Transcription Factors - chemistry, Transcription Factors - genetics, Transcription Factors - metabolism, Transfection, Yeast, Yeasts