Type 1 protein phosphatase (PP1) in the yeast Saccharomyces cerevisiae
A primary interest in our laboratory is the type 1 protein phosphatase (PP1) in the yeast Saccharomyces cerevisiae. This evolutionarily conserved enzyme dephosphorylates phosphoserine and phosphothreonine residues on many proteins in vitro and has recently been shown to have a key regulatory role in physiological responses ranging from insulin-dependent activation of glycogen synthesis to the regulation of ion channels in the brain. The specificity of PP1 is determined by auxiliary subunits that regulate the activity of the phosphatase and target the enzyme to specific subcellular compartments. We are using a combination of genetic and biochemical strategies to identify these regulatory subunits. Our recent focus has been the PP1 activity that opposes the Aurora B protein kinase. This Aurora B protein kinase is essential for proper segregation of chromosomes at mitosis. We have found that cells lacking Aurora B kinase activity rapidly die from aneuploidy. We have recently completed a genetic screen to identify mutations that compensate for a reduction in Aurora B activity. Characterization of these mutants reveal novel mutations in the PP1 phosphatase activity that opposes Aurora B, mutations in microtubule-binding components of the kinetochore, mutations in a subunit of the Cdc48/p97 chaperone-like ATPase, and a mutation in a component of the Target of Rapamycin Complex 1 (TORC1). TORC1 is a key regulator of cell growth control in response to nutritional signals. Our findings provide an effective means of tying cell growth control to the regulation of chromosome segregation.
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