| First Author | Lin T | Year | 2021 |
| Journal | J Biol Chem | Volume | 297 |
| Issue | 5 | Pages | 101264 |
| PubMed ID | 34600885 | Mgi Jnum | J:312779 |
| Mgi Id | MGI:6787301 | Doi | 10.1016/j.jbc.2021.101264 |
| Citation | Lin T, et al. (2021) Hop2 interacts with the transcription factor CEBPalpha and suppresses adipocyte differentiation. J Biol Chem 297(5):101264 |
| abstractText | CCAAT enhancer binding protein (CEBP) transcription factors (TFs) are known to promote adipocyte differentiation; however, suppressors of CEBP TFs have not been reported thus far. Here, we find that homologous chromosome pairing protein 2 (Hop2) functions as an inhibitor for the TF CEBPalpha. We found that Hop2 mRNA is highly and specifically expressed in adipose tissue, and that ectopic Hop2 expression suppresses reporter activity induced by CEBP as revealed by DNA transfection. Recombinant and ectopically expressed Hop2 was shown to interact with CEBPalpha in pull-down and coimmunoprecipitation assays, and interaction between endogenous Hop2 and CEBPalpha was observed in the nuclei of 3T3 preadipocytes and adipocytes by immunofluorescence and coimmunoprecipitation of nuclear extracts. In addition, Hop2 stable overexpression in 3T3 preadipocytes inhibited adipocyte differentiation and adipocyte marker gene expression. These in vitro data suggest that Hop2 inhibits adipogenesis by suppressing CEBP-mediated transactivation. Consistent with a negative role for Hop2 in adipogenesis, ablation of Hop2 (Hop2(-/-)) in mice led to increased body weight, adipose volume, adipocyte size, and adipogenic marker gene expression. Adipogenic differentiation of isolated adipose-derived mesenchymal stem cells showed a greater number of lipid droplet-containing colonies formed in Hop2(-/-) adipose-derived mesenchymal stem cell cultures than in wt controls, which is associated with the increased expression of adipogenic marker genes. Finally, chromatin immunoprecipitation revealed a higher binding activity of endogenous CEBPalpha to peroxisome proliferator-activated receptor gamma, a master adipogenic TF, and a known CEBPalpha target gene. Therefore, our study identifies for the first time that Hop2 is an intrinsic suppressor of CEBPalpha and thus adipogenesis in adipocytes. |
