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The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription.

Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, Downing JR, Grosveld G, Roussell MF, Gilliland DG, Lenny N, Meyers S
Mol Cell Biol. 1996 16 (4): 1349-55

PMID: 8657108 · PMCID: PMC231119 · DOI:10.1128/mcb.16.4.1349

The t(12;21) translocation is present in up to 30% of childhood B-cell acute lymphoblastic and fuses a potential dimerization motif from the ets-related factor TEL to the N terminus of AML1. The t(12;21) translocation encodes a 93-kDa fusion protein that localizes to a high-salt- and detergent-resistant nuclear compartment. This protein binds the enhancer core motif, TGTGGT, and interacts with the AML-1-binding protein, core-binding factor beta. Although TEL/AML-1B retains the C-terminal domain of AML-1B that is required for transactivation of the T-cell receptor beta enhancer, it fails to activate transcription but rather inhibits the basal activity of this enhancer. TEL/AML-1B efficiently interferes with AML-1B dependent transactivation of the T-cell receptor beta enhancer, and coexpression of wild-type TEL does not reverse this inhibition. The N-terminal TEL helix-loop-helix domain is essential for TEL/AML-1B-mediated repression. Thus, the t(12;21) fusion protein dominantly interferes with AML-1B-dependent transcription, suggesting that the inhibition of expression of AML-1 genes is critical for B-cell leukemogenesis.

MeSH Terms (16)

Base Sequence Chromosomes, Human, Pair 12 Chromosomes, Human, Pair 21 DNA-Binding Proteins Enhancer Elements, Genetic Helix-Loop-Helix Motifs Humans Leukemia Molecular Sequence Data Proto-Oncogene Proteins c-ets Recombinant Fusion Proteins Repressor Proteins Sequence Deletion Transcription, Genetic Transcription Factors Translocation, Genetic

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