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The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
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The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
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Journal Article
The Leukemia-Associated Fusion Protein MN1-TEL Blocks TEL-Specific Recognition Sequences
2012
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Binding
/ Biology
/ DNA
/ ETS Translocation Variant 6 Protein
/ Fluorescence Recovery After Photobleaching
/ Genes
/ Kinases
/ Leukemia
/ Medicine
/ Mice
/ Oncogene Proteins - genetics
/ Oncogene Proteins - metabolism
/ Oncogene Proteins, Fusion - genetics
/ Oncogene Proteins, Fusion - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-ets - genetics
/ Proto-Oncogene Proteins c-ets - metabolism
/ Repressor Proteins - genetics
