PLoS ONE (Jan 2012)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0046085
Journal volume & issue
Vol. 7, no. 9
p. e46085

Abstract

Read online

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.