TLE, the human homolog of groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation.
The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.
Imai
Y
Y
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, Bunkyo-ku, 113-8655, Japan.
Kurokawa
M
M
Tanaka
K
K
Friedman
A D
AD
Ogawa
S
S
Mitani
K
K
Yazaki
Y
Y
Hirai
H
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D019556:COS Cells; D056970:Co-Repressor Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D019272:Leukocyte Elastase; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D012097:Repressor Proteins; D014157:Transcription Factors; C493728:RUNX1 protein, human; C499043:TLE1 protein, human; C091023:gro protein, Drosophila