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PMID: 9751710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 20 ·1998-09-29 ·Pages 11590-5

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

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Armadillo Domain Proteins Basic Helix-Loop-Helix Transcription Factors Binding Sites Cell Line Co-Repressor Proteins Core Binding Factor Alpha 2 Subunit Cytoskeletal Proteins/metabolism DNA-Binding Proteins/chemistry,genetics,metabolism Drosophila/genetics,metabolism Drosophila Proteins Genes, Reporter Humans Insect Proteins/genetics,metabolism Lymphoid Enhancer-Binding Factor 1 Neoplasm Proteins Nuclear Proteins/chemistry,genetics,metabolism Protein Binding Proto-Oncogene Proteins Receptors, Antigen, T-Cell, alpha-beta/genetics,metabolism Recombinant Fusion Proteins/chemistry,genetics,metabolism Repressor Proteins/chemistry,genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Trans-Activators Transcription Factors/chemistry,genetics,metabolism Transfection beta Catenin
Chemicals
ARM protein, Drosophila Armadillo Domain Proteins Basic Helix-Loop-Helix Transcription Factors CTNNB1 protein, human Co-Repressor Proteins Core Binding Factor Alpha 2 Subunit Cytoskeletal Proteins DNA-Binding Proteins Drosophila Proteins Insect Proteins LEF1 protein, human Lymphoid Enhancer-Binding Factor 1 Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins RUNX1 protein, human Receptors, Antigen, T-Cell, alpha-beta Recombinant Fusion Proteins Repressor Proteins TLE1 protein, human Trans-Activators Transcription Factors beta Catenin gro protein, Drosophila
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Levanon D
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Goldstein R E
Bernstein Y
Tang H
Goldenberg D
Stifani S
Paroush Z
Groner Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.20.11590
Published
1998-09-29
Pages
11590-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21685
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.20.11590 PMC Full Text View journal details
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