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J. Lomako, W.M. Lomako, C.A. C. Carraway, K.L. Carraway; Prteasomal Regulation of Muc4 in Cultured Corneal Epithelium Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):884.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previous evidence indicates that the amount of Muc4/SMC in many different epithelial cells is regulated at both transcriptional and post–translational levels. This study was initiated to determine whether the level of Muc4/SMC in corneal epithelial cells depends on proteasomal degradation. Methods: Cultured rat corneal epithelial cells were treated with proteasomal inhibitors to determine their effects on Muc4/SMC levels, measured by immunobloting. Ubiquitination of Muc4/SMC was investigated by sequential immunoprecipitation and immunoblotting, and localization of Muc4/SMC within the cells was determined by confocal immunofluorescence microscopy. The effect of carbohydrate chain processing inhibitors on Muc4 levels was also investigated by immunoblotting. Results: The level of Muc4/SMC significantly increased in cultured corneal epithelial cells after treatment with proteasome inhibitors, indicating that proteasomes play role in quantity and/or quality control of Muc4/SMC in this epithelium. Transmembrane subunit (ASGP–2) of Muc4/SMC is ubiquitinated, probably as part of the proteasomal degradation mechanism. Inhibitors of N–linked carbohydrate chain processing increased proteasomal degradation, the effect of which can be partially reversed by proteasome inhibitors. Cells treated with proteasome inhibitors accumulated Muc/4SMC in intracellular inclusions resembling aggresomes. Conclusions: This is the first report indicating that Muc4/SMC is subjected in corneal epithelium to ubiquitination and proteosomal degradation. This mechanism may provide an important pathway which regulates the level of Muc4 in epithelial cells.
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