The Role of E2F4 in Adipogenesis Is Independent of Its Cell Cycle Regulatory Activity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 5; pp. 2456 - 2461
• Main Authors: Landsberg, Rebecca L., Sero, Julia E., Danielian, Paul S., Yuan, Tina L., Lee, Eunice Y., Lees, Jacqueline A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.03.2003; National Acad Sciences; The National Academy of Sciences
• Subjects: Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; Animals; Azo Compounds - pharmacology; Biological Sciences; Blood Proteins - metabolism; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Cycle; Cell cycle proteins; Cell Differentiation; Cell Division; Cellular biology; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - physiology; E2F4 Transcription Factor; Fibroblasts - metabolism; Gene expression; Gene expression regulation; Genetic mutation; Genotype; Hormones; Immunoblotting; Lipogenesis; Mice; Nuclear Proteins - metabolism; Phenotypes; Protein Binding; Proteins; Receptors, Cytoplasmic and Nuclear - metabolism; Retinoblastoma Protein - metabolism; Retinoblastoma-Like Protein p107; Retinoblastoma-Like Protein p130; Time Factors; Transcription Factors - chemistry; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0138064100

The E2F and pocket protein families are known to play an important role in the regulation of both cellular proliferation and terminal differentiation. In this study, we have used compound E2F and pocket protein mutant mouse embryonic fibroblasts to dissect the role of these proteins in adipogenesis. This analysis shows that loss of E2F4 allows cells to undergo spontaneous differentiation. The ability of E2F4 to prevent adipogenesis seems to be quite distinct from the known properties of E2F. First, it can be separated from any change in either E2F-responsive gene expression or cell cycle regulation. Second, it is a specific property of E2F4, and not other E2Fs, and it occurs independently of E2F4's ability to interact with pocket proteins. In addition, E2F4 loss does not override the differentiation defect resulting from pRB loss even though it completely suppresses the proliferation defect of Rb-/-mouse embryonic fibroblasts. This finding definitively separates the known, positive role of pRB in adipogenesis from its cell cycle function and shows that this pocket protein is required to act downstream of E2F4 in the differentiation process.