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p27kip1-independent cell cycle regulation by MYC

Oncogene volume 19, pages 4822–4827 (2000)Cite this article

Abstract

MYC transcription factors are potent stimulators of cell proliferation. It has been suggested that the CDK-inhibitor p27kip1 is a critical G1 phase cell cycle target of c-MYC. We show here that mouse embryo fibroblasts deficient for both p27kip1 and the related p21cip1 are still responsive to stimulation by c-MYC and can be arrested in G1 by a dominant negative mutant of c-MYC. This growth arrest can be overruled by ectopic expression of E2F or adenovirus E1A, but not by a mutant of E1A defective for binding to retinoblastoma family proteins. We show that fibroblasts with a genetic disruption of all three retinoblastoma family members (pRb, p107 and p130) are unresponsive to a dominant negative c-MYC mutant. These data indicate that p27kip1 is not the only rate limiting cell cycle target of c-MYC and suggest that regulation of E2F is also essential for c-MYC's mitogenic activity.

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Acknowledgements

We thank P Leder and J Roberts for generously supplying the p21 KO and p27 KO mice, respectively. B Scheijen for providing various knockout MEFs, F Michiels (Introgene, Leiden) for providing the Ad-LacZ and Ad-MadMyc adenoviruses, EAJ Reits for optimizing electroporation conditions, AS Pfauth and E Noteboom for their excellent assistance with FACS analyses. This work was funded by the Dutch Cancer Society and a Portuguese grant: PGDBM e praxis XXI to Carla Martins.

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  1. Katrien Berns, Carla Martins and Jan-Hermen Dannenberg: K Berns, C Martins and J-H Dannenberg contributed equally to the paper

Authors and Affiliations

  1. Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands' Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Katrien Berns, Jan-Hermen Dannenberg, Hein te Riele & René Bernards

  2. Division of Molecular Genetics, The Netherlands' Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Carla Martins & Anton Berns

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  1. Katrien Berns
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Berns, K., Martins, C., Dannenberg, JH. et al. p27kip1-independent cell cycle regulation by MYC. Oncogene 19, 4822–4827 (2000). https://doi.org/10.1038/sj.onc.1203879

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