PAK1, A GENE THAT CAN REGULATE P53 ACTIVITY IN YEAST

The ability of p53 protein to activate transcription is central to its tumor-suppressor function. We describe a genetic selection in Sacchar omyces cerevisiae which was used to isolate a mutant strain defective in p53-mediated transcriptional activation, The defect was partially c orrected by overexpression of a yeast gene named PAK1 (p53 activating kinase), which localizes to the left arm of chromosome IX. PAK1 is pre dicted to encode an 810-aa protein with regions of strong similarity t o previously described Ser/Thr-specific protein kinases. PAK1 sequence s upstream of the coding region are characteristic of those regulating genes involved in cell cycle control. Expression of PAK1 was associat ed with an increased specific activity of p53 in DNA-binding assays ac companied by a corresponding increase in transactivation, Thus, PAK1 i s the prototype for a class of genes that can regulate the activity of p53 in vivo, and the system described here should be useful in identi fying other genes in this class.