Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein

F. Guidez, Petrie Kevin Petrie, A. M. Ford, H. Lu, C. A. Bennett, A. MacGregor, J. Hannemann, Y. Ito, J. Ghysdael, M. Greaves, L. M. Wiedemann, A. Zelent

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in a pediatric cancer and occurs in approximately 25% of common acute lymphoblastic leukemia (cALL) cases. This rearrangement results in the in frame fusion of the 5'-region of the ETS-related gene, TEL (ETV6), to almost the entire acute myeloid leukemia 1 (AML 1)(also called CBFA2 or PEBP2AB1) locus and expression of the TEL-AML1 chimeric protein. Although AML1 stimulates transcription, TEL-AML1 functions as a repressor of some AML1 target genes. In contrast to the wild type AML1 protein, both TEL and TEL-AML1 interact with N-CoR, a component of the nuclear receptor compressor complex with histone deacetylase activity. The interaction between TEL and N-CoR requires the central region of TEL, which is retained in TEL-AML1, and TEL lacking this domain is impaired in transcriptional repression. Taken together, our results suggest that TEL-AML1 may contribute to leukemogenesis by recruiting N-CoR to AML1 target genes and thus imposing an altered pattern of their expression. (C) 2000 by the American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2557-2561
Number of pages5
JournalBlood
Volume96
Issue number7
DOIs
StatePublished - Oct 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Guidez, F., Kevin Petrie, P., Ford, A. M., Lu, H., Bennett, C. A., MacGregor, A., Hannemann, J., Ito, Y., Ghysdael, J., Greaves, M., Wiedemann, L. M., & Zelent, A. (2000). Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood, 96(7), 2557-2561. https://doi.org/10.1182/blood.v96.7.2557