Oncogenic potential of a C.elegans cdc25 gene is demonstrated by a gain-of-function allele.
In multicellular organisms, developmental programmes must integrate with central cell cycle regulation to co-ordinate developmental decisions with cell proliferation. Hyperplasia caused by deregulated proliferation without significant change to other aspects of developmental behaviour is a probable step towards full oncogenesis in many malignancies. CDC25 phosphatase promotes progression through the eukaryotic cell cycle by dephosphorylation of cyclin-dependent kinase and, in humans, different cdc25 family members have been implicated as potential oncogenes. Demonstrating the direct oncogenic potential of a cdc25 gene, we identify a gain-of-function mutant allele of the Caenorhabditis elegans gene cdc-25.1 that causes a deregulated proliferation of intestinal cells resulting in hyperplasia, while other aspects of intestinal cell function are retained. Using RNA-mediated interference, we demonstrate modulation of the oncogenic behaviour of this mutant, and show that a reduction of the wild-type cdc-25.1 activity can cause a failure of proliferation of intestinal and other cell types. That gain and loss of CDC-25.1 activity has opposite effects on cellular proliferation indicates its critical role in controlling C.elegans cell number.
Clucas
Caroline
C
The Wellcome Centre for Molecular Parasitology, The University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, Scotland, UK.
Cabello
Juan
J
Büssing
Ingo
I
Schnabel
Ralf
R
Johnstone
Iain L
IL
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D003001:Cloning, Molecular; D005799:Genes, Dominant; D018392:Genomic Imprinting; D005854:Germ Cells; D007422:Intestines / Q000166:cytology / Q000254:growth & development; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000235:genetics*
D020687:cdc25 Phosphatases