Marjolein J F W Janssen

Publications (3)13.89 Total impact

• Article: 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
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  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.
  PLoS ONE 01/2012; 7(9):e46085. · 4.09 Impact Factor
• Source

  Available from: Magda A Meester-Smoor

  Article: The ETS family member TEL binds to nuclear receptors RAR and RXR and represses gene activation.

  Magda A Meester-Smoor, Marjolein J F W Janssen, W Martijn ter Haar, Karel H M van Wely, Albert-Jan L H J Aarnoudse, Gertine van Oord, Gabrielle B A van Tilburg, Ellen C Zwarthoff
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  ABSTRACT: Retinoic acid receptor (RAR) signaling is important for regulating transcriptional activity of genes involved in growth, differentiation, metabolism and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a member of the ETS family of transcription factors, is a DNA-binding transcriptional repressor. Here, we identify TEL as a transcriptional repressor of RAR signaling by its direct binding to both RAR and its dimerisation partner, the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in two isoforms, created by the use of an alternative startcodon at amino acid 43. Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form of TEL represses RAR signaling much more efficiently. Binding studies revealed that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have shown that repression by TEL does not involve recruitment of histone deacetylases and suggest that polycomb group proteins participate in the process.
  PLoS ONE 01/2011; 6(9):e23620. · 4.09 Impact Factor
• Article: MN1 affects expression of genes involved in hematopoiesis and can enhance as well as inhibit RAR/RXR-induced gene expression.

  Magda A Meester-Smoor, Marjolein J F W Janssen, Gerard C Grosveld, Annelies de Klein, Wilfred F J van IJcken, Hannie Douben, Ellen C Zwarthoff
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  ABSTRACT: The oncoprotein meningioma 1 (MN1) is overexpressed in several subtypes of acute myeloid leukemia (AML) and overexpression was associated with a poor response to chemotherapy. MN1 is a cofactor of retinoic acid receptor/retinoic x receptor (RAR/RXR)-mediated transcription and this study identified genes in the promonocytic cell line U937 that were regulated by MN1. We found that MN1 can both stimulate and inhibit transcription. Combining MN1 expression with all-trans retinoic acid (ATRA), the ligand of the RAR/RXR dimer, showed that MN1 could both enhance and repress ATRA effects. Many of the identified genes are key players in hematopoiesis and leukemogenesis (e.g. MEIS1 and BMI1). Another interesting target is DHRS9. DHRS9 is involved in the synthesis of ATRA from vitamin A. MN1 inhibited DHRS9 expression and completely abolished its induction by ATRA. MN1 is also the target of a rare AML-causing translocation encoding the MN1-TEL protein. MN1-TEL induces expression of only a few genes and its most pronounced effect is inhibition of a large group of ATRA-induced genes including DHRS9. In conclusion, both MN1 and MN1-TEL interfere with the ATRA pathway and this might explain the differentiation block in leukemias in which these genes are involved.
  Carcinogenesis 10/2008; 29(10):2025-34. · 5.70 Impact Factor