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PMID:15060169

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Citation

Ross, DA, Rao, PK and Kadesch, T (2004) Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes. Mol. Cell. Biol. 24:3505-13

Abstract

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.

Links

PubMed PMC381674

Keywords

3T3 Cells; Adipocytes/cytology; Adipocytes/physiology; Animals; Basic Helix-Loop-Helix Transcription Factors; CCAAT-Enhancer-Binding Protein-alpha/genetics; CCAAT-Enhancer-Binding Protein-alpha/metabolism; Calcium-Binding Proteins; Cell Differentiation/physiology; Down-Regulation; Gene Expression Regulation, Developmental; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Intercellular Signaling Peptides and Proteins; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Proteins/metabolism; RNA, Small Interfering/metabolism; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Receptors, Notch; Repressor Proteins/genetics; Repressor Proteins/metabolism; Signal Transduction/physiology; Transcription Factors/genetics; Transcription Factors/metabolism

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