AIMP1 negatively regulates adipogenesis by inhibiting PPARγ

J Cell Sci. 2014 Oct 15;127(Pt 20):4483-93. doi: 10.1242/jcs.154930. Epub 2014 Aug 21.

Abstract

Adipogenesis is known to be controlled by the concerted actions of transcription factors and co-regulators. However, little is known about the mechanism of regulation of the transcription factors that control adipogenesis. In addition, the adipogenic roles of translational factors remain unclear. Here, we show that aminoacyl tRNA synthetase-interacting multifunctional protein 1 (AIMP1, also known as p43), an auxiliary factor that is associated with a macromolecular tRNA synthetase complex, negatively regulates adipogenesis through a direct interaction with the DNA-binding domain of peroxisome proliferator-activated receptor γ (PPARγ). We found that AIMP1 expression increases during adipocyte differentiation. Adipogenesis is augmented in AIMP1-deficient cells, as compared with control cells. AIMP1 exhibits high affinity for active PPARγ and interacts with the DNA-binding domain of PPARγ, thereby inhibiting its transcriptional activity. Thus, AIMP1 appears to function as a novel inhibitor of PPARγ that regulates adipocyte differentiation by preventing the transcriptional activation of PPARγ.

Keywords: AIMP1; Adipogenesis; PPARγ; tRNA synthetase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / physiology*
  • Adipogenesis / genetics*
  • Animals
  • Animals, Newborn
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Embryo, Mammalian
  • Gene Expression Regulation*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Protein Binding
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic / genetics

Substances

  • Cytokines
  • Neoplasm Proteins
  • PPAR gamma
  • RNA-Binding Proteins
  • small inducible cytokine subfamily E, member 1