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Cytokine response gene 6 induces p21 and regulates both cell growth and arrest

Oncogene volume 18, pages 6573–6582 (1999)Cite this article

Abstract

Cytokine response gene #6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis. To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb+ cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication. Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins. By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb+ cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb− and pRb+ cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21. Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.

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Acknowledgements

We thank Charles Sherr for helpful comments, and Albert Fornace, Daniel Liebermann and Hsiou-Chi Liou for critical reading of the manuscript. This work was performed in partial fulfilment of a Doctor of Philosophy degree (W Fan) from Cornell University, Weill Graduate School of Medical Sciences. Support was derived from the National Institutes of Health, NIAID grant # RO1 AI 32031-23.

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Authors and Affiliations

  1. Cornell University, Weill Medical College & Graduate School of Medical Sciences, The New York Presbyterian-Cornell Medical Center, 1300 York Avenue, New York, NY10021, USA

    Wen Fan & Kendall A Smith

  2. The Division of Immunology, Department of Medicine, The New York Presbyterian-Cornell Medical Center, 1300 York Avenue, New York, NY10021, USA

    Gunther Richter, Anna Cereseto, Carol Beadling & Kendall A Smith

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  1. Wen Fan
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Fan, W., Richter, G., Cereseto, A. et al. Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. Oncogene 18, 6573–6582 (1999). https://doi.org/10.1038/sj.onc.1203054

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