Abstract
BackgroundActivation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene. Hence, PPARs represent promising targets for cancer treatment because of their anti-proliferative and pro-apoptotic activities. Here we computationally identified PPAR binding regions in NHE1 and MnSOD. We further validated the predictions in vitro.ResultsOur results computationally predicted the presence of 2 PPRE motifs in NHE1 and 3 PPRE motifs in MnSOD. We experimentally confirmed the true motifs and their regulation by PPAR.ConclusionOur results suggest that both NHE1 and MnSOD have PPRE binding motif in their upstream/promoter region and hence are regulated by PPAR upon ligand binding.
Highlights
PPARs (Peroxisome proliferators activated Receptor) belong to the nuclear receptor super family and are ligand activated transcription factors, regulating a wide variety of genes [1]
We further investigated if peroxisome proliferator-activated receptor-g (PPARg) binds to the promoter of Na+/H+ Exchangers (NHEs) 1 and MnSOD genes at these Peroxisome Proliferator Response Elements (PPREs) motifs
PPRE motif collection It is known that the general DR1 and DR2 consensus are AGGTCA N AGGTCA (6-N-6) and AGGTCA NN AGGTCA (6-NN-6), respectively
Summary
PPARs (Peroxisome proliferators activated Receptor) belong to the nuclear receptor super family and are ligand activated transcription factors, regulating a wide variety of genes [1]. The first isoform PPAR a is expressed in tissues that play a role in fatty acid catabolism such as liver, kidney, heart, and intestine [4] This isoform is the first described receptor that is activated by peroxisome proliferators and the name [5]. Based on the cell proliferation and differentiation, the expression profile of this isoform varies Both isoforms PPAR a and b are involved in lipid utilization activities such as fatty acid oxidation, energy uncoupling reactions and response to fasting [1]. Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages They are involved in transcription regulation of genes upon activation by a ligand.
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