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Publication : Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes.

First Author  Ross DA Year  2004
Journal  Mol Cell Biol Volume  24
Issue  8 Pages  3505-13
PubMed ID  15060169 Mgi Jnum  J:89916
Mgi Id  MGI:3041923 Doi  10.1128/MCB.24.8.3505-3513.2004
Citation  Ross DA, et al. (2004) Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes. Mol Cell Biol 24(8):3505-13
abstractText  The process of adipogenesis involves a complex program of gene expression that includes down-regulation of the gene encoding Hes-1, a target of the Notch signaling pathway. To determine if Notch signaling affects adipogenesis, we exposed 3T3-L1 preadipocytes to the Notch ligand Jagged1 and found that differentiation was significantly reduced. This effect could be mimicked by constitutive expression of Hes-1. The block was associated with a complete loss of C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma) induction and could be overcome by retroviral expression of either C/EBPalpha or PPARgamma2. Surprisingly, small interfering RNA (siRNA)-mediated reduction of Hes-1 mRNA in 3T3-L1 cells also inhibited differentiation, suggesting an additional, obligatory role for Hes-1 in adipogenesis. This role may be related to our observation that both Notch signaling and Hes-1 down-regulate transcription of the gene encoding DLK/Pref-1, a protein known to inhibit differentiation of 3T3-L1 cells. The results presented in this study establish a new target downstream of the Notch-Hes-1 pathway and suggest a dual role for Hes-1 in adipocyte development.
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