Stk40 represses adipogenesis through translational control of CCAAT/enhancer-binding proteins

Academic Article


  • A better understanding of molecular regulation in adipogenesis might help the development of efficient strategies to cope with obesity-related diseases. Here, we report that CCAAT/enhancer-binding protein (C/EBP) ß and C/EBPd, two crucial pro-adipogenic transcription factors, are controlled at a translational level by serine/threonine kinase 40 (Stk40). Genetic knockout (KO) or knockdown (KD) of Stk40 leads to increased protein levels of C/EBP proteins and adipocyte differentiation in mouse embryonic fibroblasts (MEFs), fetal liver stromal cells, and mesenchymal stem cells (MSCs). In contrast, overexpression of Stk40 abolishes the enhanced C/EBP protein translation and adipogenesis observed in Stk40-KO and -KD cells. Functionally, knockdown of C/EBPß eliminates the enhanced adipogenic differentiation in Stk40-KO and -KD cells substantially. Mechanistically, deletion of Stk40 enhances phosphorylation of eIF4Ebinding protein 1, leading to increased eIF4E-dependent translation of C/EBPß and C/EBPd. Knockdown of eIF4E in MSCs decreases translation of C/EBP proteins. Moreover, Stk40-KO fetal livers display an increased adipogenic program and aberrant lipid and steroid metabolism.Collectively, our study uncovers a newrepressor of C/EBP protein translation as well as adipogenesis and provides new insights into the molecular mechanism underpinning the adipogenic program.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Yu H; He K; Wang L; Hu J; Gu J; Zhou C; Lu R; Jin Y
  • Start Page

  • 2881
  • End Page

  • 2890
  • Volume

  • 128
  • Issue

  • 15