A complex containing two transcription factors regulates peroxisome proliferation and the coordinate induction of beta-oxidation enzymes in Saccharomyces cerevisiae.
Expression of the POX1 gene, which encodes peroxisomal acyl coenzyme A oxidase in the yeast Saccharomyces cerevisiae, is tightly regulated and can be induced by fatty acids such as oleate. Previously we have shown that this regulation is brought about by interactions between trans-acting factor(s) and an upstream activating sequence (UAS1) in the POX1 promoter. We recently identified and isolated a transcription factor, Oaf1p, that binds to the UAS1 of POX1 and mediates its induction. A screening strategy has been developed and used to identify eight S. cerevisiae mutants, from three complementation groups, that are defective in the oleate induction of POX1. Characterization of one such mutant led to the identification of Oaf2p, a protein that is 39% identical to Oaf1p. Oaf1p and Oaf2p form a protein complex that is required for the activation of POX1 and FOX3 and for proliferation of peroxisomes. We propose a model in which these two transcription factors heterodimerize and mediate this activation process. The mutants that we have isolated, and further identification of the corresponding defective genes, provide us with an opportunity to characterize the mechanisms involved in the coordinate regulation of peroxisomal beta-oxidation enzymes.
Karpichev
I V
IV
Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, New York 10029, USA.
Luo
Y
Y
Marians
R C
RC
Small
G M
GM
D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics; D042962:Acyl-CoA Oxidase; D000595:Amino Acid Sequence; D001483:Base Sequence; D002374:Catalase / Q000235:genetics; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology*; D005800:Genes, Fungal / Q000235:genetics; D005816:Genetic Complementation Test; D008830:Microbodies / Q000201:enzymology* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation; D019301:Oleic Acid / Q000494:pharmacology*; D010088:Oxidoreductases / Q000235:genetics; D012331:RNA, Fungal / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; C100530:PIP2 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D019301:Oleic Acid; D010088:Oxidoreductases; D002374:Catalase; D042962:Acyl-CoA Oxidase; C467991:POX1 protein, S cerevisiae; D000101:Acetyl-CoA C-Acetyltransferase