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Oncogenic potential of the DNA replication licensing protein CDT1

Oncogene volume 21, pages 1150–1158 (2002)Cite this article

Abstract

The expression of a gene, designated as Retroviral insertion site (Ris)2, was activated by retroviral DNA integration in an immortalized primitive erythroid cell line, EB-PE. Ris2 was also expressed at high levels in all human tumor cell lines analysed. Consistently, NIH3T3 fibroblasts overexpressing Ris2 formed tumors in Rag2−/− mice when injected subcutaneously. The putative RIS2 protein shows a high sequence similarity to Xenopus CDT1, Drosophila DUP, and human CDT1, a newly identified DNA replication licensing protein, suggesting that Ris2 is a mouse homologue of CDT1. Cells overexpressing Ris2/Cdt1 exhibited a quicker entry into S phase when released from serum starvation compared to controls. Our results suggest that CDT1, an essential licensing protein for DNA replication, can function as an oncogene in mammals.

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Acknowledgements

We thank Douglas Dean, Steven Dowdy, and Linda Van Dyk for helpful discussion with cell cycle analyses. We thank Kathy Sheehan for help with the antibody generation, Hyung Kyoo Kang with the help of Western blot analyses, Paul Allen and Barry Sleckman for rag−2−/− mice, and Darren Kraemelmeyer for animal husbandry. We would like to thank Rainer Brachmann, Yun Shin Chung, Marco Colonna, Douglas Dean, Igor Roninson, Robert Schreiber and Wen Jie Zhang for helpful comments on the manuscript.

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Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA

    Elizabeth Arentson, Patrick Faloon, Junghee Seo, Joey M Studts, Daved H Fremont & Kyunghee Choi

  2. Department of Biological Sciences, Ajou University, Suwon, Korea

    Junghee Seo & Eunpyo Moon

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  1. Elizabeth Arentson
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  2. Patrick Faloon
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Correspondence to Kyunghee Choi.

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Arentson, E., Faloon, P., Seo, J. et al. Oncogenic potential of the DNA replication licensing protein CDT1. Oncogene 21, 1150–1158 (2002). https://doi.org/10.1038/sj.onc.1205175

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