RESUMEN
The cyclin-dependent protein kinase (CDK) encoded by CDC28 is the master regulator of cell division in the budding yeast Saccharomyces cerevisiae. By mechanisms that, for the most part, remain to be delineated, Cdc28 activity controls the timing of mitotic commitment, bud initiation, DNA replication, spindle formation, and chromosome separation. Environmental stimuli and progress through the cell cycle are monitored through checkpoint mechanisms that influence Cdc28 activity at key cell cycle stages. A vast body of information concerning how Cdc28 activity is timed and coordinated with various mitotic events has accrued. This article reviews that literature. Following an introduction to the properties of CDKs common to many eukaryotic species, the key influences on Cdc28 activity-cyclin-CKI binding and phosphorylation-dephosphorylation events-are examined. The processes controlling the abundance and activity of key Cdc28 regulators, especially transcriptional and proteolytic mechanisms, are then discussed in detail. Finally, the mechanisms by which environmental stimuli influence Cdc28 activity are summarized.
Asunto(s)
Proteína Quinasa CDC28 de Saccharomyces cerevisiae/genética , Proteína Quinasa CDC28 de Saccharomyces cerevisiae/metabolismo , Regulación Fúngica de la Expresión Génica , Saccharomyces cerevisiae/enzimología , Proteína Quinasa CDC28 de Saccharomyces cerevisiae/antagonistas & inhibidores , Ciclo Celular , Ciclinas/metabolismo , Fosforilación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Transcripción GenéticaRESUMEN
The Pharmacogenetics and Pharmacogenomics Knowledge Base, PharmGKB (http://www.pharmgkb.org), curates pharmacogenetic and pharmacogenomic information to generate knowledge concerning the relationships among genes, drugs, and diseases, and the effects of gene variation on these relationships. PharmGKB curators collect information on genotype-phenotype relationships both from the literature and from the deposition of primary research data into our database. Their goal is to catalyze pharmacogenetic and pharmacogenomic research.