Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.
The eight-twenty-one (ETO) homologues, represented by ETO, myeloid transforming gene-related protein 1 (MTGR1) and myeloid transforming gene chromosome 16 (MTG16), are nuclear repressor proteins. ETO is part of the fusion protein acute myeloid leukaemia (AML)1-ETO, resulting from the translocation (8;21). Similarly, MTG16 is disrupted to become part of AML1/MTG16 in t(16;21). The aberrant expression of these chimeras could affect interplay between ETO homologues and contribute to the leukaemogenic process. We investigated possible interactions between the ETO homologues. Ectopic co-expression in COS-cells resulted in heterodimerisation of the various ETO homologues suggesting that they may co-operate. Similarly, the chimeric oncoprotein AML1-ETO interacted with both MTGR1 and MTG16. However, results from cell lines endogenously expressing more than one ETO homologue did not demonstrate co-precipitation. Results from IP-Western and size determination by gel filtration of deletion mutants expressed in COS-cells, indicated an important role of the HHR domain for oligomerisation. A role was also suggested for the Nervy domain in the homologue interactions. Our results suggest that ETO homologues can interact with each other as well as with AML1-ETO, although it is unclear as to what extent these interactions occur in vivo.
Lindberg
Sofia Rondin
SR
Department of Hematology, C14, BMC, S-221 84 Lund, Sweden. sofia.rondin_lindberg@hematologi.lu.se
Olsson
André
A
Persson
Ann-Maj
AM
Olsson
Inge
I
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D004347:Drug Interactions; D017353:Gene Deletion; D015870:Gene Expression; D007163:Immunosorbent Techniques; D007938:Leukemia; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; D012097:Repressor Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D017385:Sequence Homology; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C110408:CBFA2T2 myeloid-transforming gene-related protein; C115744:CBFA2T3 protein, human; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins