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 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.
Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
W Martijn
WM
ter Haar
Magda A
MA
Meester-Smoor
Karel H M
KH
van Wely
Claudia C M M
CC
Schot
Marjolein J F W
MJ
Janssen
Bart
B
Geverts
Jacqueline
J
Bonten
Gerard C
GC
Grosveld
Adriaan B
AB
Houtsmuller
Ellen C
EC
Zwarthoff
D000818:Animals; D036681:Fluorescence Recovery After Photobleaching; D051379:Mice; D009010:Monte Carlo Method; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein
D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C501081:Mn1 protein, mouse