The RAS-adenylate cyclase pathway and cell cycle control in Saccharomyces cerevisiae.
The cell cycle of Saccharomyces cerevisiae contains a decision point in G1 called 'start', which is composed of two specific sites. Nutrient-starved cells arrest at the first site while pheromone-treated cells arrest at the second site. Functioning of the RAS-adenylate cyclase pathway is required for progression over the nutrient-starvation site while overactivation of the pathway renders the cells unable to arrest at this site. However, progression of cycling cells over the nutrient-starvation site does not appear to be triggered by the RAS-adenylate cyclase pathway in response to a specific stimulus, such as an exogenous nutrient. The essential function of the pathway appears to be limited to provision of a basal level of cAMP. cAMP-dependent protein kinase rather than cAMP might be the universal integrator of nutrient availability in yeast. On the other hand stimulation of the pathway in glucose-derepressed yeast cells by rapidly-fermented sugars, such as glucose, is well documented and might play a role in the control of the transition from gluconeogenic growth to fermentative growth. The initial trigger of this signalling pathway is proposed to reside in a 'glucose sensing complex' which has both a function in controlling the influx of glucose into the cell and in activating in addition to the RAS-adenylate cyclase pathway all other glucose-induced regulatory pathways in yeast. Two crucial problems remaining to be solved with respect to cell cycle control are the nature of the connection between the RAS-adenylate cyclase pathway and nitrogen-source induced progression over the nutrient-starvation site of 'start' and second the nature of the downstream processes linking the RAS-adenylate cyclase pathway to Cyclin/CDC28 controlled progression over the pheromone site of 'start'.
Thevelein
J M
JM
Laboratorium voor Moleculaire Celbiologie, Katholieke Universiteit te Leuven, Heverlee, Flanders, Belgium.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D015513:Oncogene Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D015398:Signal Transduction
D015513:Oncogene Proteins; D000262:Adenylyl Cyclases