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PLOS ONE 2012

The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences

DOI: 10.1371/journal.pone.0046085

W. Martijn ter Haar, Magda A. Meester-Smoor, Karel H. M. van Wely, Claudia C. M. M. Schot, Marjolein J. F. W. Janssen, Bart Geverts, Jacqueline Bonten, Gerard C. Grosveld, Adriaan B. Houtsmuller, Ellen C. Zwarthoff

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Abstract:

The leukemia-associated fusion protein MN1-TEL combines the transcription-activating domains of MN1 with the DNA-binding domain of the transcriptional repressor TEL. Quantitative photobleaching experiments revealed that ~20% of GFP-tagged MN1 and TEL is transiently immobilised, likely due to indirect or direct DNA binding, since transcription inhibition abolished immobilisation. Interestingly, ~50% of the MN1-TEL fusion protein was immobile with much longer binding times than unfused MN1 and TEL. MN1-TEL immobilisation was not observed when the TEL DNA-binding domain was disrupted, suggesting that MN1-TEL stably occupies TEL recognition sequences, preventing binding of factors required for proper transcription regulation, which may contribute to leukemogenesis.

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