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

oleh: 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

Format: Article
Diterbitkan: Public Library of Science (PLoS) 2012-01-01

Deskripsi

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.