Jarno Drost

Publications (4)58.34 Total impact

• Source

  Available from: Reuven Agami

  Article: Gene regulation and tumor suppression by the bromodomain-containing protein BRD7.

  Fiamma Mantovani, Jarno Drost, P Mathijs Voorhoeve, Giannino Del Sal, Reuven Agami
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  ABSTRACT: Oncogene-induced senescence (OIS) is a cellular defense mechanism against excessive mitogenic signaling and tumorigenesis. One of the major pathways required for OIS is the p53 tumor suppressor pathway. Consequently, many human tumors harbor p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We recently identified BRD7 as a potential tumor suppressor gene acting as a transcriptional cofactor for p53, affecting histone acetylation, p53 acetylation, and promoter activity on a subset of p53 target genes. We further found low BRD7 expression specifically in a subgroup of human breast tumors harboring wild-type, but not mutant, p53 and showed that one of the responsible mechanisms is deletion of the BRD7 gene locus. Here we further discuss the role of BRD7 as a cofactor in transcriptional regulation and highlight its role as a tumor suppressor via association with p53 and other tumor suppressor proteins.
  Cell cycle (Georgetown, Tex.) 07/2010; 9(14):2777-81. · 5.36 Impact Factor
• Source

  Available from: Jos Jonkers

  Article: BRD7 is a candidate tumour suppressor gene required for p53 function.

  Jarno Drost, Fiamma Mantovani, Francesca Tocco, Ran Elkon, Anna Comel, Henne Holstege, Ron Kerkhoven, Jos Jonkers, P Mathijs Voorhoeve, Reuven Agami, Giannino Del Sal
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  ABSTRACT: Oncogene-induced senescence is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations and others show a dysfunctional p53 pathway, frequently by unknown mechanisms. Here we identify BRD7 (bromodomain-containing 7) as a protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. In human breast tumours harbouring wild-type, but not mutant, p53 the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300 and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation and promoter activity. Thus, BRD7 suppresses tumorigenicity by serving as a p53 cofactor required for the efficient induction of p53-dependent oncogene-induced senescence.
  Nature Cell Biology 03/2010; 12(4):380-9. · 19.49 Impact Factor
• Article: Transformation locked in a loop.

  Jarno Drost, Reuven Agami
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  ABSTRACT: During neoplastic transformation, cells can promote their own growth by activating proto-oncogenes. Reporting in Cell, Iliopoulos et al. (2009) now show that in certain cell types, a transient oncogenic signal is sufficient to induce neoplastic transformation and to maintain it through a positive feedback loop driven by the inflammatory cytokine interleukin-6.
  Cell 11/2009; 139(4):654-6. · 32.40 Impact Factor
• Source

  Available from: Reuven Agami

  Article: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors.

  P Mathijs Voorhoeve, Carlos le Sage, Mariette Schrier, Ad J M Gillis, Hans Stoop, Remco Nagel, Ying-Poi Liu, Josyanne van Duijse, Jarno Drost, Alexander Griekspoor, Eitan Zlotorynski, Norikazu Yabuta, Gabriella De Vita, Hiroshi Nojima, Leendert H J Looijenga, Reuven Agami
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  ABSTRACT: Endogenous small RNAs (miRNAs) regulate gene expression by mechanisms conserved across metazoans. While the number of verified human miRNAs is still expanding, only few have been functionally annotated. To perform genetic screens for novel functions of miRNAs, we developed a library of vectors expressing the majority of cloned human miRNAs and created corresponding DNA barcode arrays. In a screen for miRNAs that cooperate with oncogenes in cellular transformation, we identified miR-372 and miR-373, each permitting proliferation and tumorigenesis of primary human cells that harbor both oncogenic RAS and active wild-type p53. These miRNAs neutralize p53-mediated CDK inhibition, possibly through direct inhibition of the expression of the tumorsuppressor LATS2. We provide evidence that these miRNAs are potential novel oncogenes participating in the development of human testicular germ cell tumors by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53.
  Advances in experimental medicine and biology 02/2007; 604:17-46. · 1.09 Impact Factor