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  ETO, but not Leukemogenic Fusion Protein AML1/ETO, Augments RBP-Jκ/SHARP-Mediated Repression of Notch Target Genes

Salat, D., Liefke, R., Wiedemann, J., Borggrefe, T., & Oswald, F. (2008). ETO, but not Leukemogenic Fusion Protein AML1/ETO, Augments RBP-Jκ/SHARP-Mediated Repression of Notch Target Genes. Molecular and Cellular Biology, 28, 3502-3512.

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 Creators:
Salat, Daniela, Author
Liefke, Robert1, Author              
Wiedemann, Jörg, Author
Borggrefe, Tilman1, Author              
Oswald, Franz, Author
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Abstract: Notch is a transmembrane receptor that determines cell fates and pattern formation in all animal species. After specific ligand binding, the intracellular part of Notch is cleaved off and translocates to the nucleus, where it targets the DNA binding protein RBP-Jκ. In the absence of Notch, RBP-Jκ represses Notch target genes by recruiting a corepressor complex. We and others have previously identified SHARP as one component of this complex. Here, we show that the corepressor ETO as well as the leukemogenic fusion protein AML1/ETO directly interacts with SHARP, that ETO is part of the endogenous RBP-Jκ-containing corepressor complex, and that ETO is found at Notch target gene promoters. In functional assays, corepressor ETO, but not AML1/ETO, augments SHARP-mediated repression in an histone deacetylase-dependent manner. Furthermore, either the knockdown of ETO or the overexpression of AML1/ETO activates Notch target genes. Therefore, we propose that AML1/ETO can disturb the normal, repressive function of ETO at Notch target genes. This activating (or derepressing) effect of AML1/ETO may contribute to its oncogenic potential in myeloid leukemia.

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Language(s): eng - English
 Dates: 2008-05
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 402232
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Title: Molecular and Cellular Biology
  Alternative Title : Mol. Cell. Biol.
Source Genre: Journal
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Pages: - Volume / Issue: 28 Sequence Number: - Start / End Page: 3502 - 3512 Identifier: -