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

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

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

Year: 2012
DOI identifier: 10.1371/journal.pone.0046085
OAI identifier: oai:repub.eur.nl:66882

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