The nuclear receptor co-repressor (N-CoR) utilizes repression domains I and III for interaction and co-repression with ETO.
The acute human leukemias are associated with the presence of chimeric gene products that arise from spontaneous chromosomal translocations. The t(8;21) translocation gene product led to the discovery of the Eight Twenty-One (ETO) gene. When fused to RUNX1, ETO is thought to mediate the formation of a repressive complex at RUNX1-dependent genes. ETO has also been found to act as a co-repressor of the promyelocytic zinc finger and Bcl-6 oncoproteins, suggesting that it may play a common role as a transcriptional co-repressor leading to human disease. An analysis of ETO-mediated repression revealed that one of the key binding partners of ETO is the nuclear receptor co-repressor (N-CoR). It is shown that two highly conserved domains of ETO interact with repression domains I and III of N-CoR. One of the ETO domains displays significant homology to Drosophila TAF(II)110, whereas the other is a predicted zinc binding motif that engages a conserved PPLXP motif in repression domain III of N-CoR. Together, these domains of ETO cooperate in repression with N-CoR and the binding sites in N-CoR overlap with those for other repressive factors. Thus, ETO has the potential to participate in a number of repressive complexes, which can be distinguished by their binding partners and target genes.
Lausen
Jörn
J
Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Cho
Seongeun
S
Liu
Shaohua
S
Werner
Milton H
MH
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D017353:Gene Deletion; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D056971:Nuclear Receptor Co-Repressor 1; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D012694:Serine; D004247:DNA; D005982:Glutathione Transferase; D015032:Zinc; D003545:Cysteine