| Notes
|
The protein encoded by this gene is a member of the peroxisome proliferator-activated receptor (PPAR) family. PPARs are nuclear hormone receptors that bind peroxisome proliferators and control the size and number of peroxisomes produced by cells. PPARs mediate a variety of biological processes, and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer. This protein is a potent inhibitor of ligand-induced transcription activity of PPAR delta and PPAR gamma. It may function as an integrator of transcription repression and nuclear receptor signaling. The expression of this gene is found to be elevated in colorectal cancer cells. The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein related to APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation. Alternatively spliced transcript variants encoding distinct isoforms have been reported. 11beta-HSD2 is an additional target for PPAR delta, which may regulate human placental function. 4 polymorphisms were found: -409C/T (promoter, +73C/T (exon 1), +255A/G (exon 3), & +294T/C (exon 4). An interaction with the PPAR alpha L162V polymorphism was also detected for several lipid parameters. PPARD plays a role in cholesterol metabolism. COX-2 immunopositivity was significantly associated with PPARbeta and PPARgamma immunoreactivity. Microvessel density was significantly higher among PPARbeta-immunoreactive squamous cell carcinomas. Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates triglyceride accumulation in keratinocytes. PPARdelta signaling pathways are interconnected at the level of cross-regulation of their respective transcription factor mRNA levels. Positive associations of PPAR-delta polymorphisms with fasting plasma glucose and BMI detected in nondiabetic control subjects. Results suggest that peroxisome proliferator-activated receptor beta overexpression is not an inherent property of breast cancer cell lines, but it may play a role through activation of downstream genes (PPARbeta). The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells. This study was performed to determine whether specific activation of PPARdelta has direct effects on insulin action in skeletal muscle. Data contribute to a better understanding of the mechanisms by which PPARs regulate VEGF expression in bladder cancer cells. Differential regulation of vascular endothelial growth factor expression in bladder cancer cells (peroxisome proliferative activated receptor, beta). Gene regulation by PPARdelta in the uterine cells uniquely responds to SRC-2, N-CoR, SMRT, or RIP140, and these interactions may be operative during implantation when these cofactors are abundantly expressed. Results implicate PPAR-delta in the regulation of intestinal adenoma growth. The ligand-independent tight control of the position of the PPAR helix 12 provides an effective alternative for establishing an interaction with CoA proteins.
|