Peroxisome response element

Peroxisome Proliferator-Activated Receptors. Figure 2 Binding of PPAR RXR heterodimers to DR1 PPRE-responsive elements. Abbreviations DR1, a direct repeat organization of the A/GGGTCA hexamer half-site separated by a single nucleotide spacer. 

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that bind to DNA response elements (PPREs) and control multiple aspects of lipid metabolism. Individual members of this family of zinc-finger proteins are activated by a variety of natural and xenobiotic dgands, including ... 

Miyamoto, T, Kaneko, A., Kakizawa, T, Yajima, H., Kamijo, K., Sekine, R., Hiramatsu, K., Nishii, Y, Hashimoto, T. Hashizume, K. (1997) Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element. J. biol. Chem., Ill, 7752-7758... 

Woodyatt, N.J., Lambe, K.G, Myers, K.A., Tugwood, J.D. Roberts, R.A. (1999) The peroxisome proliferator (PP) response element upstream of the human acyl CoA oxidase gene is inactive among a sample human population significance for species differences in response to PPs. Carcinogenesis, 20, 369-372... 

Figure 5.36 Mechanism of the receptor-mediated induction of CYP4A by a chemical such as the drug clofibrate. The inducer-receptor (PPAR) complex enters the nucleus, binds with RXR, and the complex binds to the receptor response elements in the CYP gene. This induces the production of CYP4A mRNA, which leads to the production of CYP4A protein and functional enzyme. Alternatively, the drug may perturb lipid metabolism leading to increases in a lipid(s), which will bind to the receptor and cause the same response. Abbreviations PPAR, peroxisome proliterator-activated receptor RXR, retinoid X receptor.

The receptor protein (52 kDa) is a member of the steroid hormone receptor superfamily, which has a DNA-binding as well as ligand-binding domain. Another receptor, the retinoid X receptor is also involved, and after binding of the peroxisome proliferator, the two receptors form a heterodimer. This binds to a regulatory DNA sequence known as the peroxisome proliferator response element. The end result of the interaction between peroxisome proliferators and this system is that genes are switched on, leading to increases in synthesis (induction) of both microsomal and peroxisomal enzymes and possibly hyperplasia. 

A novel peroxisome proliferator-activated receptor responsive element-luciferase reporter mouse reveals gender specificity of peroxisome proliferator-activated receptor activity in liver. Mol Endocrinol. 21(2), 388-400. 

Tugwood,J. D., Issemann, I., Anderson, R. G., Bundell, K. R., McPheat, W. L., and Green, S. (1992). The mouse peroxisome proliferator activated receptor recognizes a response element in the 5 flanking sequence of the rat acyl CoA oxidase gene. EMBOJ. 11, 433-439. 

Varanasi U, Chu R, Huang Q, et al. 1996. Identification of a peroxisome proliferator-responsive element upstream ofthe human peroxisomal fatty acyl coenzyme A oxidase gene. J Biol Chem271 2147-2155. 

Figure 2.7. The complex pathways and processes involved in fat catabolism in vertebrate tissues such as cardiac and skeletal muscles. FFAs arrive at the cell boundary either via VLDL or albumin-associated and enter the cell either by simple diffusion or through transporters. In the cytosol, FFAs are bound by FABPs, which increase the rate and amount of FFA that can be transferred to sites of utilization. Shorter chain FFAs are converted to acetylCoA in peroxisomes longer chain FFAs are directly transferred to mitochondria (via a complex system involving acylcarnitines) as long-chain acylCoA derivatives these enter the /6-oxidation spiral and are released as acetylCoA for entrance into the Krebs or citric acid cycle in the mitochondrial matrix. Fatty acid receptors (FARs) in the nucleus bind to fatty acid response elements (FAREs) and in turn regulate the production of enzymes in their own metabolism. (Modified from Veerkamp and Maatman, 1995.)...

Figure 3 The PPAR family and its DNA properties, (a) The murine PPAR subfamily. The DNA and ligand-binding domains are indicated. Numbers represent percentage amino acid identity, (b) The PPARs bind to DR-1-type DNA response elements as heterodimers with RXR. The PPAR/RXR heterodimer can be activated by ligands for either PPAR or RXR. (Reproduced from Kliewer SA, Xu HE, Lambert MH, and Willson TM (2001) Peroxisome proliferator-activated receptors From genes to physiology. Recent Progress in Hormone Research 56 239-265, with permission from The Endocrine Society.)...

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