The leukemia-associated fusion protein MN1-TEL blocks TEL-specific recognition sequences.

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.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e46085 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23049943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mn1 protein, mouse
• Oncogene Proteins
• Oncogene Proteins, Fusion
• Proto-Oncogene Proteins c-ets
• Repressor Proteins
• Trans-Activators
• Tumor Suppressor Proteins

Topics

• Animals
• Fluorescence Recovery After Photobleaching
• Mice
• Monte Carlo Method
• NIH 3T3 Cells
• Oncogene Proteins (genetics, metabolism)
• Oncogene Proteins, Fusion (genetics, metabolism)
• Protein Binding
• Proto-Oncogene Proteins c-ets (genetics, metabolism)
• Repressor Proteins (genetics, metabolism)
• Trans-Activators
• Tumor Suppressor Proteins
• ETS Translocation Variant 6 Protein