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The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle

Oncogene volume 24, pages 7337–7345 (2005)Cite this article

Abstract

The retinoblastoma protein (pRB) is encoded by the RB1 gene whose promoter contains several putative binding sites for ICBP90 (Inverted CCAAT box Binding Protein of 90 kDa), a transcriptional regulator of the topoisomerase IIα gene. ICBP90 has two consensus binding sites for pRB in its primary sequence. Here, we show that pRB and ICBP90 co-immunoprecipitate in cell extracts of proliferating human lung fibroblasts and of proliferating or confluent Jurkat cells. GST pull-down assays and immunocytochemistry, after cell synchronization in late G1 phase, confirmed this interaction. Overexpression of ICBP90 induces downregulation of pRB expression in lung fibroblasts as a result of mRNA decrease. DNA chromatin immunoprecipitation experiment shows that ICBP90 binds to the RB1 gene promoter under its methylated status. Overexpression of ICBP90 increases the S and G2/M phase cell fractions of serum-starved lung fibroblasts as assessed by flow cytometry analysis and increases topoisomerase IIα expression. Together, these results show that ICBP90 regulates pRB at the protein and gene transcription levels, thus favoring the entry into the S phase of the cells. We propose that ICBP90 overexpression, found in cancer cells, is involved in the altered checkpoint controls occurring in cancerogenesis.

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Acknowledgements

The work was supported by the association Ligue contre le Cancer, Comité du Haut-Rhin.

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Authors and Affiliations

  1. Inserm UMR S392, Faculté de Pharmacie, 74 route du Rhin, BP 60024, Illkirch Cedex, 67401, France

    Michaël Jeanblanc, Marc Mousli, Raphaël Hopfner, Kawtar Bathami, Abdul-Qader Abbady, Eric Mathieu & Christian Bronner

  2. CNRS UMR7034, Faculté de Pharmacie, 74 route du Rhin, BP 60024, Illkirch Cedex, 67401, France

    Michaël Jeanblanc, Christian D Muller & Christian Bronner

  3. EMI INSERM 0014, Faculté de Médecine, 9 avenue de la Forêt de Haye, Vandoeuvre-lès-Nancy, 54511, France

    Nadine Martinet

  4. Laboratoire de Biochimie-Immunochimie, Centre Hospitalier de Belfort-Montbéliard, 14 rue de Mulhouse, Belfort Cedex, 90016, France

    Jean-Claude Siffert

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  1. Michaël Jeanblanc
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Correspondence to Christian Bronner.

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Jeanblanc, M., Mousli, M., Hopfner, R. et al. The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle. Oncogene 24, 7337–7345 (2005). https://doi.org/10.1038/sj.onc.1208878

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