Role of Peroxisome Proliferator-Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

Figure 1

Schematic structure of the human PPAR gene. The human PPAR gene is located on chromosome 3, band 3p25, and is composed of at least 11 exons that give rise to 9 transcript variants. Expression of PPAR involves differential promoter usage in combination with alternative splicing and polyadenylation site selection. The relative positions of the four known PPAR promoters are designated as P1-P4. The noncoding exons A1, A^′, and A2 are depicted by boxes in different shades of gray or in black and white checked. These exons contribute to the 5^′ UTR of transcripts 1-1d, 3 and 1tr. The transcript variants 1-1d, 3, and 4 encode the PPAR1 isoform. Exon B (diagonal blue and white hatched box) encodes the 28 additional amino acids found at the amino terminus of human PPAR2; the mouse PPAR2 exon B encodes 30 amino acids. Exons 1–6 (light blue boxes) are common in all PPAR1 transcripts and when they are spliced to exon B encode full-length PPAR2. Two additional exon regions have been recently identified, exon 3^′ (horizontal light blue and white hatched box) and exon 4^′ (small light blue box). Inclusion of either of these coding regions in the processed mRNA transcript results in truncated PPAR1 proteins lacking the ligand binding domain (1tr and ORF4, resp.). The sizes of the exon boxes approximate the relative lengths of each exon; however, the introns (depicted as straight lines) are not drawn to scale. The positions of the stop codons are depicted by the hexagonal red stop signs.