Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization.
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.
Denicourt
C
C
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Québec, Canada.
Legault
P
P
McNabb
F-A C
FA
Rassart
E
E
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D013347:Subcellular Fractions / Q000378:metabolism / Q000502:physiology; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D018631:ras Proteins