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

Citation

Guidez F, Petrie K, Ford AM, Lu H, Bennett CA, MacGregor A, Hannemann J, Ito Y, Ghysdael J, Greaves M, Wiedemann LM & 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), pp. 2557-2561. http://www.bloodjournal.org/content/96/7/2557.article-info

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 (AML1) (also calledCBFA2orPEBP2AB1) 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 corepressor 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.

Journal
Blood: Volume 96, Issue 7