Karpichev I V, Luo Y, Marians R C, Small G M
Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, New York 10029, USA.
Mol Cell Biol. 1997 Jan;17(1):69-80. doi: 10.1128/MCB.17.1.69.
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.
POX1基因在酿酒酵母中编码过氧化物酶体酰基辅酶A氧化酶，其表达受到严格调控，并且可被油酸等脂肪酸诱导。我们之前已经表明，这种调控是由反式作用因子与POX1启动子中的上游激活序列（UAS1）之间的相互作用所引起的。我们最近鉴定并分离出一种转录因子Oaf1p，它与POX1的UAS1结合并介导其诱导作用。已经开发出一种筛选策略并用于鉴定来自三个互补组的八个酿酒酵母突变体，这些突变体在POX1的油酸诱导方面存在缺陷。对其中一个这样的突变体的表征导致鉴定出Oaf2p，一种与Oaf1p有39%同源性的蛋白质。Oaf1p和Oaf2p形成一种蛋白质复合物，该复合物是激活POX1和FOX3以及过氧化物酶体增殖所必需的。我们提出了一个模型，其中这两个转录因子异源二聚化并介导这一激活过程。我们分离出的突变体以及对相应缺陷基因的进一步鉴定，为我们提供了一个机会来表征参与过氧化物酶体β氧化酶协同调控的机制。
