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W. Guo, F. Shang, Q. Liu, A. Taylor; Regulation of the Ubiquitin-Proteasome Pathway (UPP) During Lens Cell Differentiation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):951.
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Purpose: To investigate the regulation of the UPP during lens cell differentiation and determine the potential role for the UPP in controlling lens differentiation. Methods: The rat lens epithelial explants were induced to differentiate into fiber cells by treatment with bFGF. Levels and activities of the enzymes involved in ubiquitination (E1, E2 or Ubc, E3) and substrates for the UPP (such as p21 and p27) were monitored during the differentiation process. Results: Explants treated with bFGF showed characteristics of lens fibers, including expression of large quantities of crystallins and removal of organelles. Whereas levels of E1 remained constant during the differentiation process, the level of Ubc1 increased ~2-fold and thiol ester form of Ubc1 increased ~3-fold upon 7 days of bFGF treatment. Levels of Ubc2 also increased upon FGF treatment, with most of the Ubc2 being found in thiol ester form. Although levels of total Ubc3 and Ubc7 remained unchanged, the proportions of Ubc3 and Ubc7 in the thiol ester form were significantly higher in the bFGF-treated explants. Levels of Ubc4/5 and Ubc9 also increased significantly upon treatment with bFGF, and >50% of the Ubc9 was found in the thiol ester form in the bFGF-treated explants. In contrast, levels of Cul1, the backbone of E3 (SCF), decreased 50-70% in bFGF-treated explants. Consistent with the decreased Cul1 level, the levels of p21 and p27 were higher in bFGF treated explants. Conclusions: The data show that different components of the UPP are differentially regulated during lens cell differentiation. The general up-regulation of UPP components upon differentiation is consistent with a role for the pathway in the differentiation process. However, the accumulation of several E2s in the thiol ester form may result from the down-regulation of the respective E3s, such as SCF. The dramatic increase in levels of Ubc4/5 in the differentiating fibers suggests that these E2s may play a role for lens fiber maturation, such as removal of organelles.
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