The focus of this application is on adipocyte differentiation. Adipocyte differentiation requires the coordinated expression of numerous gene involved in growth. Early during the differentiation process, adipocyte precursors along with many other cell types, are required to re-enter the cell cycle and undergo a clonal expansion phase prior to growth arrest and terminal differentiation. The pathways involved in regulation of these early cell cycle events are largely unknown. Studies in tumor cells as well as non-malignant cells suggest that members of the retinoblastoma family of proteins play important roles in regulating cell cycle progression, particularly through their interaction with the E2F family of transcription factors. The PI has identified a regulation in p130 and p107 expression in differentiating 3T3-L1 cells (a model of adipocyte differentiation). This """"""""p130:p107 switch"""""""" correlates with early mitotic clonal expansion. They also present data suggesting that disruption of the p130:p107 switch by TNF alpha may explain the well described TNF alpha-induced inhibition of adipogenesis. They also present data that pRb is involved in transcriptional control of adipocyte genes. Based on these findings, they hypothesize that the retinoblastoma family of proteins is involved in adipocyte differentiation. The application proposes experiments designed to examine mechanisms through which these interactions occur.
| Ross, Ashley S; Tsang, Rocky; Shewmake, Kris et al. (2008) Expression of p107 and p130 during human adipose-derived stem cell adipogenesis. Biochem Biophys Res Commun 366:927-31 |
| Burton, Gregory R; Nagarajan, Radhakrishnan; Peterson, Charlotte A et al. (2004) Microarray analysis of differentiation-specific gene expression during 3T3-L1 adipogenesis. Gene 329:167-85 |
| Burton, Gregory R; McGehee Jr, Robert E (2004) Identification of candidate genes involved in the regulation of adipocyte differentiation using microarray-based gene expression profiling. Nutrition 20:109-14 |
| Burton, Gregory R; Guan, Yu; Nagarajan, Radhakrishnan et al. (2002) Microarray analysis of gene expression during early adipocyte differentiation. Gene 293:21-31 |
| Taylor-Jones, Jane M; McGehee, Robert E; Rando, Thomas A et al. (2002) Activation of an adipogenic program in adult myoblasts with age. Mech Ageing Dev 123:649-61 |
| Liu, Kenian; Guan, Yu; MacNicol, Melanie C et al. (2002) Early expression of p107 is associated with 3T3-L1 adipocyte differentiation. Mol Cell Endocrinol 194:51-61 |
| Prince, Audra M; May, Julie S; Burton, Gregory R et al. (2002) Proteasomal degradation of retinoblastoma-related p130 during adipocyte differentiation. Biochem Biophys Res Commun 290:1066-71 |
| Guan, Yu; Taylor-Jones, Jane M; Peterson, Charlotte A et al. (2002) p130/p107 expression distinguishes adipogenic potential in primary myoblasts based on age. Biochem Biophys Res Commun 296:1340-5 |
| May, J S; Prince, A M; Lyle, R E et al. (2001) Antisense suppression of p107 inhibits 3T3-L1 adipocyte differentiation. Biochem Biophys Res Commun 283:837-42 |
| Cowherd, R M; Lyle, R E; McGehee Jr, R E (1999) Molecular regulation of adipocyte differentiation. Semin Cell Dev Biol 10:3-10 |
