Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

ETO, but not leukemogenic fusion protein AML1/ETO, augments RBP-Jkappa/SHARP-mediated repression of notch target genes.

http://www.ncbi.nlm.nih.gov/pubmed/18332109

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-Jkappa. In the absence of Notch, RBP-Jkappa 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-Jkappa-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.

Pubmed ID: 18332109 RIS Download

Mesh terms: Animals | Basic Helix-Loop-Helix Transcription Factors | Binding Sites | Cell Cycle Proteins | Cell Line | Cell Line, Tumor | Core Binding Factor Alpha 2 Subunit | DNA-Binding Proteins | Gene Expression | HeLa Cells | Homeodomain Proteins | Humans | Immunoglobulin J Recombination Signal Sequence-Binding Protein | Leukemia, Myeloid | Mice | Oncogene Proteins, Fusion | Promoter Regions, Genetic | Proto-Oncogene Proteins | Receptors, Notch | Recombinant Fusion Proteins | Repressor Proteins | Signal Transduction | Transcription Factors | Transcription, Genetic | Two-Hybrid System Techniques

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.