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Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation

Oncogene volume 19, pages 2447–2454 (2000)Cite this article

Abstract

Members of the cdc25 family are protein phosphatases that play pivotal roles in cell cycle progression. Cdc25A has been shown to be a critical regulator of the G1/S transition of mammalian cells and to be a myc-target gene with oncongenic properties. We investigated the regulation of cdc25A during terminal differentiation using myeloblastic leukemia M1 cells, that can be induced to undergo differentiation into macrophages by interleukin-6 (IL-6) treatment. In this report it is shown that cdc25A protein is degraded by the ubiquitin-proteasome machinery in both terminally differentiating and cycling cells. Cdc25A was found to have two major peaks of accumulation during cell cycle progression, one in G1 and the other in S/G2. Evidence was obtained that degradation of cdc25A by the ubiquitin-proteasome machinery in terminally differentiating myeloid cells is accelerated compared to cycling cells. Moreover, deregulated expression of c-myc in M1 cells, which had been previously shown to block terminal differentiation, was also found to block IL-6 induced degradation of cdc25A.

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Acknowledgements

We thank Dr Xavier Grana for critical reading of the manuscript and Dr Dale Haines for advice. This work was supported by National Institute of Health grant 1RO1CA51168 (B Hoffman) and 1RO1CA4316 (D Liebermann).

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  1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N. Broad Street, Philadelphia, 19140, Pennsylvania, PA, USA

    Rosa Bernardi, Dan A Liebermann & Barbara Hoffman

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  1. Rosa Bernardi
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  2. Dan A Liebermann
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Bernardi, R., Liebermann, D. & Hoffman, B. Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation. Oncogene 19, 2447–2454 (2000). https://doi.org/10.1038/sj.onc.1203564

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