| First Author | Yu H | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 15 | Pages | 2881-90 |
| PubMed ID | 26065429 | Mgi Jnum | J:232960 |
| Mgi Id | MGI:5780512 | Doi | 10.1242/jcs.170282 |
| Citation | Yu H, et al. (2015) Stk40 represses adipogenesis through translational control of CCAAT/enhancer-binding proteins. J Cell Sci 128(15):2881-90 |
| abstractText | 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) beta and C/EBPdelta, 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/EBPbeta eliminates the enhanced adipogenic differentiation in Stk40-KO and -KD cells substantially. Mechanistically, deletion of Stk40 enhances phosphorylation of eIF4E-binding protein 1, leading to increased eIF4E-dependent translation of C/EBPbeta and C/EBPdelta. 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 new repressor of C/EBP protein translation as well as adipogenesis and provides new insights into the molecular mechanism underpinning the adipogenic program. |
