title: In vitro transcriptional activation by a metabolic intermediate: activation by Leu3 depends on alpha-isopropylmalate.
abstract: In the absence of the leucine biosynthetic precursor alpha-isopropylmalate (alpha-IPM), the yeast LEU3 protein (Leu3p) binds DNA and acts as a transcriptional repressor in an in vitro extract. Addition of alpha-IPM resulted in a dramatic increase in Leu3p-dependent transcription. The presence of alpha-IPM was also required for Leu3p to compete effectively with another transcriptional activator, GAL4/VP16, for limiting transcription factors. Therefore, the addition of alpha-IPM appears to convert a transcriptional repressor into an activator. This represents an example in eukaryotes of direct transcriptional regulation by a small effector molecule.
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907.
authors.forename: J Y
authors.initials: JY
authors.lastname: Sze
authors.forename: M
authors.initials: M
authors.lastname: Woontner
authors.forename: J A
authors.initials: JA
authors.lastname: Jaehning
authors.forename: G B
authors.initials: GB
authors.lastname: Kohlhaw
mesh_terms: D001667:Binding, Competitive; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D005656:Fungal Proteins / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal; D008293:Malates / Q000494:pharmacology*; D012097:Repressor Proteins / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C063667:LEU3 protein, S cerevisiae; D008293:Malates; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C005906:alpha-isopropylmalate