High impact information on FOX2

• Growth of a yeast fox2sps19Delta mutant in which Fox2p was exchanged with rat peroxisomal multifunctional enzyme type 1 on trans-9,trans-12 linolelaidic acid medium gave credence to this theory [1].
• The gene encoding the multifunctional protein (MFP) of peroxisomal beta-oxidation in Saccharomyces cerevisiae was isolated from a genomic library via functional complementation of a fox2 mutant strain [2].
• Substitutions within the carboxyl-terminal tripeptide (Ala----Gly and Lys----Gln) supported targeting of HDE to peroxisomes of C. albicans but not of S. cerevisiae [3].
• We have investigated the regulation of expression of the gene (HDE), encoding the peroxisomal trifunctional enzyme hydratase-dehydrogenase-epimerase (HDE), of the diploid yeast Candida tropicalis [4].
• The gene (HDE) encoding the peroxisomal trifunctional enzyme, hydratase-dehydrogenase-epimerase, of the yeast Candida tropicalis, was cloned and its nucleotide sequence is reported [5].

Biological context of FOX2

• In contrast to its counterparts in yeasts, the Neurospora MFP does not have a C-terminal sequence resembling the SKL motif involved in protein targeting to microbodies [6].
• A partial gene duplication is believed to have occurred in the evolution of the HDE gene [7].
• The HDE cDNA (HDE) has a single open reading frame of 2718 nt, encoding a protein of 905 amino acids, not including the initiator methionine [7].
• We now describe the optimum parameters for administration of MFP to obtain cellular immunity [as measured by the cytotoxic T cell precursor (CTLp) frequency] [8].

Anatomical context of FOX2

• Deletion and mutational analyses were used to determine the regions within HDE which are essential for its targeting to peroxisomes [3].
• We have previously reported preclinical studies in mice of the human mucin 1 (MUC1) antigen covalently linked to the yeast cell-wall mannan polysaccharide (MFP), and shown strong cellular responses of the T1 type using mice [8].

Associations of FOX2 with chemical compounds

• Seven yeast polypeptides similar to human 17betaHSDs were identified: when expressed in yeast, only AYR1 (1-acyl dihydroxyacetone phosphate reductase) increased A/enediol accumulation, while the hydroxyacyl-CoA dehydrogenase Fox2p, highly homologous to human 17betaHSD4, oxidized A/enediol to DHEA [9].
• Dehydroepiandrosterone (DHEA) metabolism in Saccharomyces cerevisiae expressing mammalian steroid hydroxylase CYP7B: Ayr1p and Fox2p display 17beta-hydroxysteroid dehydrogenase activity [9].
• The increase in HDE activity in C. tropicalis cells grown in oleic acid medium as opposed to glucose medium is due, at least in part, to increased HDE-specific mRNA levels [7].

Analytical, diagnostic and therapeutic context of FOX2

• Molecular cloning, sequencing and sequence analysis of the fox-2 gene of Neurospora crassa encoding the multifunctional beta-oxidation protein [6].
• We present the molecular cloning and sequencing of genomic and cDNA clones of the fox-2 gene of Neurospora crassa, encoding the multifunctional beta-oxidation protein (MFP) [6].
• The cellular location of HDE was determined by subcellular fractionation followed by Western blot analysis of peroxisomal and cytosolic fractions using antiserum specific for HDE [3].
• A recombinant was confirmed to encode HDE by hybridization-selection translation and immunoprecipitation [7].

References