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

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 indirec...

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Detalles Bibliográficos
Autores principales: ter Haar, W. Martijn, Meester-Smoor, Magda A., van Wely, Karel H. M., Schot, Claudia C. M. M., Janssen, Marjolein J. F. W., Geverts, Bart, Bonten, Jacqueline, Grosveld, Gerard C., Houtsmuller, Adriaan B., Zwarthoff, Ellen C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458806/
https://www.ncbi.nlm.nih.gov/pubmed/23049943
http://dx.doi.org/10.1371/journal.pone.0046085
Descripción
Sumario: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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