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

Ditsa Levanon, Robert E. Goldstein, Yael Bernstein, Hua Tang, Dalia Goldenberg, Stefano Stifan, Ze'ev Paroush, Yoram Groner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

415 Scopus citations

Abstract

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-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF- 1:β-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.

Original languageAmerican English
Pages (from-to)11590-11595
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number20
DOIs
StatePublished - 29 Sep 1998

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