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

Author

  • Sofia Rondin Lindberg
  • André Olsson
  • Ann-Maj Persson
  • Inge Olsson

Summary, in English

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.

Publishing year

2003

Language

English

Pages

439-447

Publication/Series

European Journal of Haematology

Volume

71

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1600-0609