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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization

C Denicourt1, P Legault, F-A C McNabb

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

Oncogene
|September 18, 2007
PubMed

Insights

A novel truncated cyclin D2 protein, found in some leukemias and normal tissues, can transform cells when combined with activated Ras. This truncated cyclin D2, present in both mouse and human samples, localizes to the cytoplasm.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • A novel 17 kDa truncated isoform of cyclin D2 was previously identified in Graffi murine leukemia virus-induced leukemias.
  • This truncated form arises from alternative splicing of the mouse cyclin D2 gene due to retroviral integration in the Gris1 locus.
  • Similar truncated cyclin D2 forms have been observed in human samples, including brain tumors.

Purpose of the Study:

  • To investigate the functional consequences of truncated cyclin D2 expression.
  • To determine the cellular localization and kinase interaction of the truncated cyclin D2 isoform.
  • To assess the oncogenic potential of truncated cyclin D2 in cellular transformation assays.

Main Methods:

  • Co-expression of mouse and human truncated cyclin D2 with activated Ras in primary mouse embryo fibroblasts (MEF).
  • Cellular localization studies using transfected cells.
  • Analysis of cyclin-dependent kinase (CDK) interactions and pRb phosphorylation.
  • Detection of alternatively spliced cyclin D2 mRNA in human brain tumors.

Main Results:

  • Both mouse and human truncated cyclin D2 proteins can transform MEFs when co-expressed with activated Ras.
  • The truncated cyclin D2 localizes exclusively to the cytoplasm of transfected cells.
  • While interacting with CDKs, the truncated protein is a poor catalyst of pRb phosphorylation.
  • An alternatively spliced cyclin D2 mRNA was detected in some human brain tumors.

Conclusions:

  • Truncated cyclin D2 exhibits oncogenic potential, contributing to cellular transformation in conjunction with activated Ras.
  • Cytoplasmic localization and altered kinase activity of truncated cyclin D2 suggest a distinct mechanism of action compared to the full-length protein.
  • The presence of truncated cyclin D2 in both experimental and human cancers highlights its potential role in tumorigenesis.

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