Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.

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Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins. / Rondin Lindberg, Sofia; Olsson, André; Persson, Ann-Maj; Olsson, Inge.

In: European Journal of Haematology, Vol. 71, No. 6, 2003, p. 439-447.

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Rondin Lindberg, Sofia ; Olsson, André ; Persson, Ann-Maj ; Olsson, Inge. / Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins. In: European Journal of Haematology. 2003 ; Vol. 71, No. 6. pp. 439-447.

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TY - JOUR

T1 - Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins.

AU - Rondin Lindberg, Sofia

AU - Olsson, André

AU - Persson, Ann-Maj

AU - Olsson, Inge

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1046/j.0902-4441.2003.00166.x

DO - 10.1046/j.0902-4441.2003.00166.x

M3 - Article

VL - 71

SP - 439

EP - 447

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 1600-0609

IS - 6

ER -