Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human.
BACKGROUND
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. 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.


RESULTS
Our 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.


CONCLUSIONS
Our 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.
Venkatachalam
Gireedhar
G
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. bchgv@nus.edu.sg
Kumar
Alan Prem
AP
Yue
Loo Ser
LS
Pervaiz
Shazib
S
Clement
Marie Veronique
MV
Sakharkar
Meena Kishore
MK
D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003198:Computer Simulation; D006801:Humans; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D027682:Cation Transport Proteins; D047495:PPAR gamma; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C490998:SLC9A1 protein, human