Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization.
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Denicourt C, Legault P, McNabb FA, Rassart E
Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization.
Oncogene. 2008 Feb 21;27(9):1253-62. doi: 10.1038/sj.onc.1210750. Epub 2007 Sep 17.
- PubMed ID
- 17873913 [ View in PubMed]
- 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.