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Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated

Eric S Tien1, John W Davis, John P Vanden Heuvel

  • 1Center for Molecular Toxicology and Carcinogenesis and Department of Veterinary Science, Pennsylvania State University, University Park, Pennsylvania 16802, USA.

The Journal of Biological Chemistry
|March 31, 2004
PubMed

Insights

The CREB-binding protein/p300-interacting transactivator with ED-rich tail 2 (CITED2) coactivates peroxisome proliferator-activated receptor alpha (PPARα). CITED2 influences cell proliferation and gene expression related to angiogenesis and hypoxic response.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Regulation

Background:

  • Nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs), regulate gene transcription through protein-protein interactions.
  • Identifying novel interacting proteins is crucial for understanding PPAR function.

Purpose of the Study:

  • To identify novel PPAR-interacting proteins.
  • To characterize the functional role of CITED2 as a coactivator for PPARs.
  • To investigate the involvement of CITED2 and PPARα in cellular processes like proliferation and hypoxic response.

Main Methods:

  • cDNA expression library screening using bacterially expressed PPARα.
  • Interaction cloning to identify PPARα-associated proteins.
  • Transient transfection reporter assays to assess coactivator activity.
  • Stable overexpression and small inhibitor RNA-mediated repression in mouse hepatocytes.
  • Microarray analysis and real-time PCR to evaluate gene expression changes.

Main Results:

  • CITED2 was identified as a PPARα-interacting protein, binding predominantly to the ligand-binding domain.
  • CITED2 acted as a dose-dependent coactivator for PPARα and PPARγ, but not PPARβ.
  • Overexpression of CITED2 increased hepatocyte proliferation.
  • CITED2 modulated the expression of genes involved in angiogenesis and hypoxic response in response to PPARα ligands.

Conclusions:

  • CITED2 is a coactivator of PPARα.
  • CITED2 and PPARα may play a role in the signaling pathways regulating hypoxic response and angiogenesis.

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