PAK1, a gene that can regulate p53 activity in yeast

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6062-6066
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number13
DOIs
StatePublished - Jun 20 1995

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Yeasts
Transcriptional Activation
Genes
Genetic Selection
Cell Cycle Checkpoints
Protein Kinases
Saccharomyces cerevisiae
Proteins
Phosphotransferases
Chromosomes
DNA
Neoplasms

Keywords

  • phosphorylation
  • posttranslational modification
  • transactivation
  • tumor suppressor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

PAK1, a gene that can regulate p53 activity in yeast. / Thiagalingam, Sam; Kinzler, Kenneth W; Vogelstein, Bert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 13, 20.06.1995, p. 6062-6066.

Research output: Contribution to journalArticle

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N2 - 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.

AB - 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.

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