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 Saccharomyces cerevisiae which was used to isolate a mutant strain defective in p53-mediated transcriptional activation. The defect was partially corrected by overexpression of a yeast gene named PAK1 (p53 activating kinase), which localizes to the left arm of chromosome IX. PAK1 is predicted to encode an 810-aa protein with regions of strong similarity to previously described Ser/Thr-specific protein kinases. PAK1 sequences upstream of the coding region are characteristic of those regulating genes involved in cell cycle control. Expression of PAK1 was associated with an increased specific activity of p53 in DNA-binding assays accompanied by a corresponding increase in transactivation. Thus, PAK1 is 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 identifying other genes in this class.
Thiagalingam
S
S
Johns Hopkins Oncology Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Kinzler
K W
KW
Vogelstein
B
B
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D017931:DNA Primers; D004251:DNA Transposable Elements; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016158:Genes, p53; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*; D014466:Ultraviolet Rays
D017931:DNA Primers; D004251:DNA Transposable Elements; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D005020:Ethyl Methanesulfonate; C094326:PRK1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases