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Gene Review

LEU3  -  Leu3p

Saccharomyces cerevisiae S288c

Synonyms: L9324.1, Regulatory protein LEU3, YLR451W
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High impact information on LEU3


Biological context of LEU3

  • Expression is restored to near-normal levels when the leu3 deletion cells are transformed with a LEU3-bearing plasmid [4].
  • Methylation interference footprinting experiments show that LEU3 makes symmetrical contacts with the conserved bases that lie in the major groove [5].
  • First, the expression of a GDH1-lacZ fusion gene is three- to sixfold lower in a strain lacking the LEU3 gene than in an isogenic LEU3+ strain [4].
  • Disruption of LEU3 was performed also with a diploid and shown to be nonlethal by tetrad analysis [6].
  • The leu3 marker was mapped to chromosome XII by the spo11 method [6].

Anatomical context of LEU3


Associations of LEU3 with chemical compounds

  • LEU3 of Saccharomyces cerevisiae encodes an 886-amino-acid polypeptide that regulates transcription of a group of genes involved in leucine biosynthesis and has been shown to bind specifically to a 114-base-pair DNA fragment of the LEU2 upstream region (P. Friden and P. Schimmel, Mol. Cell. Biol. 7:2707-2717, 1987) [5].
  • In vivo and in vitro studies have shown that activation by Leu3 requires the presence of alpha-isopropylmalate [4].
  • Following identification of a UASLEU-homologous sequence in the promoter of GDH1, the gene encoding NADP(+)-dependent glutamate dehydrogenase, we demonstrate that Leu3 specifically interacts with this UASLEU element [4].
  • To determine which portion of the LAC9 DNA-binding domain mediates sequence recognition, we replaced the C6 zinc finger, amino acids adjacent to the carboxyl side of the zinc finger, or both with the analogous region from the Saccharomyces cerevisiae PPR1 or LEU3 protein [8].
  • LEU3 proteins with a mutation at Cys47 were very poor activators which could not be rescued by supplying Zn(II) to the growth medium [9].

Physical interactions of LEU3

  • Subdivision of the LEU2 5' region established that the LEU3-dependent DNA-binding activity interacted with the segment which had the previously reported homology with LEU1 [10].
  • The presence of a Leu3p binding site in the BAP2 promoter is required for full promoter activity on synthetic complete medium [11].
  • Fusion of the 30 C-terminal residues of Leu3 to the DNA-binding domain of the Gal4 protein created a strong cross-species activator, demonstrating that the short C-terminal region is not only required but also sufficient for transcriptional activation [12].

Enzymatic interactions of LEU3

  • Strains containing a disrupted leu3 allele were constructed by deleting 0.7-kb of LEU3 DNA and inserting the yeast HIS3 gene in its place [6].

Regulatory relationships of LEU3

  • The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation [4].
  • A sequence resembling the GC-rich palindrome motif identified in the 5' region of S. cerevisiae LEU2 gene as the binding site for the transcription activating factor encoded by the LEU3 gene was found at the promoter region [13].
  • The capacity of Leu3p to activate BAP2 transcription correlates with conditions that affect the level of alpha-isopropyl malate [11].

Other interactions of LEU3

  • The decrease in GDH1 expression in leu3 null cells is reflected in a diminished specific activity of NADP(+)-dependent glutamate dehydrogenase [4].
  • Linkage to ura4 by about 44 centiMorgans places leu3 on the right arm of this chromosome [6].
  • ILV2 upstream deletion analyses and high-copy transformation of the positive regulatory locus LEU3 ruled out the possibility of LEU3 protein binding palindromes mediating the branched chain amino acid dependent auxotrophy [14].
  • The transcriptional regulator Leu3p is not involved in the induction of BAP3 expression, but may act as a repressor of BAP3 expression in the absence of leucine, as can be inferred from a transcriptional analysis in a Deltaleu3 mutant [15].
  • Neither Stp1p nor Leu3p appear to bind to the UASaa, at least in vitro, as judged from gel retardation assays [15].

Analytical, diagnostic and therapeutic context of LEU3


  1. In vitro transcriptional activation by a metabolic intermediate: activation by Leu3 depends on alpha-isopropylmalate. Sze, J.Y., Woontner, M., Jaehning, J.A., Kohlhaw, G.B. Science (1992) [Pubmed]
  2. Transcriptional corepression in vitro: a Mot1p-associated form of TATA-binding protein is required for repression by Leu3p. Wade, P.A., Jaehning, J.A. Mol. Cell. Biol. (1996) [Pubmed]
  3. A novel DNA binding motif for yeast zinc cluster proteins: the Leu3p and Pdr3p transcriptional activators recognize everted repeats. Hellauer, K., Rochon, M.H., Turcotte, B. Mol. Cell. Biol. (1996) [Pubmed]
  4. The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation. Hu, Y., Cooper, T.G., Kohlhaw, G.B. Mol. Cell. Biol. (1995) [Pubmed]
  5. LEU3 of Saccharomyces cerevisiae activates multiple genes for branched-chain amino acid biosynthesis by binding to a common decanucleotide core sequence. Friden, P., Schimmel, P. Mol. Cell. Biol. (1988) [Pubmed]
  6. Cloning, disruption and chromosomal mapping of yeast LEU3, a putative regulatory gene. Brisco, P.R., Cunningham, T.S., Kohlhaw, G.B. Genetics (1987) [Pubmed]
  7. Purification and structural characterization of transcriptional regulator Leu3 of yeast. Sze, J.Y., Kohlhaw, G.B. J. Biol. Chem. (1993) [Pubmed]
  8. The C6 zinc finger and adjacent amino acids determine DNA-binding specificity and affinity in the yeast activator proteins LAC9 and PPR1. Witte, M.M., Dickson, R.C. Mol. Cell. Biol. (1990) [Pubmed]
  9. Manipulation of the 'zinc cluster' region of transcriptional activator LEU3 by site-directed mutagenesis. Bai, Y.L., Kohlhaw, G.B. Nucleic Acids Res. (1991) [Pubmed]
  10. LEU3 of Saccharomyces cerevisiae encodes a factor for control of RNA levels of a group of leucine-specific genes. Friden, P., Schimmel, P. Mol. Cell. Biol. (1987) [Pubmed]
  11. Transcriptional regulation of the Saccharomyces cerevisiae amino acid permease gene BAP2. Nielsen, P.S., van den Hazel, B., Didion, T., de Boer, M., Jørgensen, M., Planta, R.J., Kielland-Brandt, M.C., Andersen, H.A. Mol. Gen. Genet. (2001) [Pubmed]
  12. Transcriptional regulator Leu3 of Saccharomyces cerevisiae: separation of activator and repressor functions. Sze, J.Y., Remboutsika, E., Kohlhaw, G.B. Mol. Cell. Biol. (1993) [Pubmed]
  13. Cloning and sequence analysis of the LEU2 homologue gene from Pichia anomala. De la Rosa, J.M., Pérez, J.A., Gutiérrez, F., González, J.M., Ruiz, T., Rodríguez, L. Yeast (2001) [Pubmed]
  14. Branched chain amino acid regulation of the ILV2 locus in Saccharomyces cerevisiae. Xiao, W., Rank, G.H. Genome (1990) [Pubmed]
  15. Regulation of expression of the amino acid transporter gene BAP3 in Saccharomyces cerevisiae. De Boer, M., Bebelman, J.P., Gonçalves, P.M., Maat, J., Van Heerikhuizen, H., Planta, R.J. Mol. Microbiol. (1998) [Pubmed]
  16. Regulation of yeast LEU2. Total deletion of regulatory gene LEU3 unmasks GCN4-dependent basal level expression of LEU2. Brisco, P.R., Kohlhaw, G.B. J. Biol. Chem. (1990) [Pubmed]
  17. Yeast regulatory protein LEU3: a structure-function analysis. Zhou, K.M., Bai, Y.L., Kohlhaw, G.B. Nucleic Acids Res. (1990) [Pubmed]
  18. Detection of leucine-independent DNA site occupancy of the yeast Leu3p transcriptional activator in vivo. Kirkpatrick, C.R., Schimmel, P. Mol. Cell. Biol. (1995) [Pubmed]
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