Control of cyclin C levels during development of Dictyostelium.
BACKGROUND
Cdk8 and its partner cyclin C form part of the mediator complex which links the basal transcription machinery to regulatory proteins. The pair are required for correct regulation of a subset of genes and have been implicated in control of development in a number of organisms including the social amoeba Dictyostelium discoideum. When feeding, Dictyostelium amoebae are unicellular but upon starvation they aggregate to form a multicellular structure which develops into a fruiting body containing spores. Cells in which the gene encoding Cdk8 has been deleted fail to enter aggregates due to a failure of early gene expression.


RESULTS
We have monitored the expression levels of cyclin C protein during development and find levels decrease after the multicellular mound is formed. This decrease is triggered by extracellular cAMP that, in turn, is working in part through an increase in intracellular cAMP. The loss of cyclin C is coincident with a reduction in the association of Cdk8 with a high molecular weight complex in the nucleus. Overexpression of cyclin C and Cdk8 lead to an increased rate of early development, consistent with the levels being rate limiting.


CONCLUSIONS
Overall these results show that both cyclin C and Cdk8 are regulated during development in response to extracellular signals and the levels of these proteins are important in controlling the timing of developmental processes. These findings have important implications for the role of these proteins in controlling development, suggesting that they are targets for developmental signals to regulate gene expression.
Greene
David M
DM
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Hsu
Duen-Wei
DW
Pears
Catherine J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D005591:Chemical Fractionation; D000242:Cyclic AMP / Q000378:metabolism; D056745:Cyclin C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016366:Open Reading Frames / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D056745:Cyclin C; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D056850:Cyclin-Dependent Kinase 8