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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Bibliographic Details
Published in:PloS one 2012-09, Vol.7 (9), p.e46085-e46085
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Binding
Biology
Care and treatment
Computer Science
Deoxyribonucleic acid
DNA
ETS Translocation Variant 6 Protein
Fluorescence Recovery After Photobleaching
Fusion protein
Fusion proteins
Gene regulation
Genes
Genetic aspects
Immobilization
Kinases
Leukemia
Leukemogenesis
Medicine
Mice
Monte Carlo Method
Monte Carlo simulation
NIH 3T3 Cells
Oncogene Proteins - genetics
Oncogene Proteins - metabolism
Oncogene Proteins, Fusion - genetics
Oncogene Proteins, Fusion - metabolism
Pathology
Photobleaching
Physiological aspects
Properties
Protein Binding
Proteins
Proto-Oncogene Proteins c-ets - genetics
Proto-Oncogene Proteins c-ets - metabolism
Recognition
Recovery (Medical)
Repressor Proteins - genetics
Repressor Proteins - metabolism
Risk factors
Trans-Activators
Transcription (Genetics)
Transcription factors
Tumor Suppressor Proteins
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0046085