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Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization

Oncogene volume 27, pages 1253–1262 (2008)Cite this article

Abstract

We have previously reported the identification of a novel 17 kDa truncated isoform of the cyclin D2 activated in 13% of the leukemias induced by the Graffi murine leukemia retrovirus. Retroviral integration in the Gris1 locus causes an alternative splicing of the mouse cyclin D2 gene and expression of a truncated protein of 159 amino acids that is detected at high levels in the Gris1 tumors and also in normal mouse tissues mainly the brain and ovaries. A truncated form of the cyclin D2 was also found in human. We show here that both mouse- and human-truncated cyclin D2 are able to transform primary mouse embryo fibroblasts (MEF) when co-expressed with an activated Ras protein. The truncated cyclin D2 localizes only to the cytoplasm of transfected cells. It has retained the ability to interact with cyclin-dependent kinases (CDKs), although it is a poor catalyst of pRb phosphorylation. Interestingly, the presence of a similar, alternatively spliced cyclin D2 mRNA was also detected in some human brain tumors.

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Acknowledgements

We thank the Arthur and Sonia Labatt Brain Tumour Research Center (http://www.sickkids.ca/BTRC/ Toronto, Canada) and Dr Abhijit Guha for the gift of human tumor tissues. This work was supported by grant FRN 37994 from the Canadian Institutes of Health Research and by La Société de recherche sur le Cancer. CD is a recipient of a FCAR PhD scholarship.

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  1. C Denicourt and P Legault: These authors contributed equally to this work.

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  1. Département des Sciences Biologiques, Laboratoire de Biologie Moléculaire, Université du Québec à Montréal, Québec, Canada

    C Denicourt, P Legault, F-A C McNabb & E Rassart

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  1. C Denicourt
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  2. P Legault
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  4. E Rassart
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Correspondence to E Rassart.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Denicourt, C., Legault, P., McNabb, FA. et al. Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization. Oncogene 27, 1253–1262 (2008). https://doi.org/10.1038/sj.onc.1210750

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