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S. M. Plafker, K. S. Plafker, K. M. Farjo; The Human Ubiquitin Conjugating Enzyme, UBE2E3, Is Required for Proliferation of Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2434. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to determine if the highly conserved ubiquitin conjugating enzyme, UBE2E3, is required for the proliferation of human retinal pigment epithelial (RPE) cells.
Small interfering RNAs (siRNAs) targeting UBE2E3 expression were introduced into immortalized, non-transformed, human RPEs. The consequence of UBE2E3 knockdown on proliferation was measured by multiple assays and markers of cell cycle progression.
Our data reveal that UBE2E3 localizes to the nucleus of normal, human RPE tissue culture cells. Depletion of the enzyme using siRNA resulted in an exit from the cell cycle. This exit was accompanied by loss of the proliferation marker Ki-67, an increase in the cyclin-dependent kinase inhibitor, p27Kip1, and an increase in cell area. Rescue experiments confirmed the specificity of the RNA interference.
This report is the first identification of a specific ubiquitin conjugating enzyme required for RPE proliferation. Similar cellular changes have been observed in rodent models of RPE development and maturation, thus implicating UBE2E3 as a key player in modulating the balance between RPE proliferation and terminal differentiation.
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