Role of the peroxisome proliferator-activated receptor in cytochrome P450 4A gene regulation

Eric F. Johnson (Lead / Corresponding author), Colin N.A. Palmer, Keith J. Griffin, Mei Hui Hsu

    Research output: Contribution to journalReview article

    167 Citations (Scopus)

    Abstract

    Cytochrome P450s of the 4A subfamily generally catalyze the ω̄- hydroxylation of fatty acids. The induction of P450 4A enzymes by peroxisome proliferators or fatty acids is mediated by peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear receptor family that regulates the expression of genes that control fatty acid synthesis, storage, and catabolism. PPARs bind as heterodimers with another member of the nuclear receptor family, the retinoid X receptor (RXR), to peroxisome proliferator response elements (PPREs) in the P450 4A1 and 4A6 genes. PPREs comprise two overlapping motifs for nuclear receptor binding. One motif consists of an imperfect, direct repeat of two copies of the nuclear receptor core binding site, AGGTCA, separated by a single nucleotide (a DR1 motif) that is recognized by other dimeric nuclear receptor complexes such as HNF-4 or ARP- 1. A consensus sequence flanking the DR1 motif together with the 5' core binding site of the DR1 motif constitutes a second, overlapping motif resembling recognition elements for monomeric nuclear receptors, such as Rev- ErbA and the melatonin receptors. PPARs bind to the latter motif. The tripartite nature of PPREs together with imperfections in the core sites of DR1 motif confers specificity for PPARGα/RXRα binding to PPREs relative to other nuclear receptors.

    Original languageEnglish
    Pages (from-to)1241-1248
    Number of pages8
    JournalFASEB Journal
    Volume10
    Issue number11
    DOIs
    Publication statusPublished - 1 Sep 1996

    Keywords

    • CYP4A
    • fatty acid ω̄-hydroxylase
    • PPAR

    Fingerprint Dive into the research topics of 'Role of the peroxisome proliferator-activated receptor in cytochrome P450 4A gene regulation'. Together they form a unique fingerprint.

  • Cite this