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

. 1996 Apr;16(4):1349-55.

doi: 10.1128/MCB.16.4.1349.

W Sun, J N Davis, T Golub, S Shurtleff, A Buijs, J R Downing, G Grosveld, M F Roussell, D G Gilliland, N Lenny, S Meyers

Affiliations

• PMID: 8657108
• PMCID: PMC231119
• DOI: 10.1128/MCB.16.4.1349

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

S W Hiebert et al. Mol Cell Biol. 1996 Apr.

Abstract

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.

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