Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.
Fiche publication
Date publication
octobre 2000
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUIDEZ Fabien
Tous les auteurs :
Guidez F, Petrie K, Ford AM, Lu H, Bennett CA, MacGregor A, Hannemann J, Ito Y, Ghysdael J, Greaves M, Wiedemann LM, Zelent A
Lien Pubmed
Résumé
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 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 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.
Mots clés
Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, genetics, Gene Expression, Humans, Immunosorbent Techniques, Nuclear Proteins, genetics, Nuclear Receptor Co-Repressor 1, Oncogene Proteins, Fusion, genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma, genetics, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Recombinant Proteins, Repressor Proteins, genetics, Transcription Factors, genetics, Transfection, ETS Translocation Variant 6 Protein
Référence
Blood. 2000 10 1;96(7):2557-61