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

BMC Genomics. 2009 Dec 3;10 Suppl 3(Suppl 3):S5. doi: 10.1186/1471-2164-10-S3-S5.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cation Transport Proteins / chemistry*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Computer Simulation
  • Humans
  • Molecular Sequence Data
  • PPAR gamma / chemistry
  • PPAR gamma / metabolism*
  • Promoter Regions, Genetic
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / chemistry*
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism
  • Superoxide Dismutase / chemistry*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Cation Transport Proteins
  • PPAR gamma
  • SLC9A1 protein, human
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers
  • Superoxide Dismutase
  • superoxide dismutase 2