Sumoylation controls retinal progenitor proliferation by repressing cell cycle exit in Xenopus laevis

Precisely controlled progenitor proliferation is essential for normal development. However, molecular mechanisms, which control the correct timing of cell cycle withdrawal during development, have been poorly understood. We show here that ubc9, a sumo-conjugating enzyme, controls the cell cycle exit of retinal progenitors. We found that ubc9 is highly expressed in retinal progenitors and stem cells in Xenopus embryos. Ubc9 physically and functionally associates with Xenopus hmgb3, which is required for retinal cell proliferation, and prolonged expression of ubc9 and hmgb3 results in suppression of the cell cycle exit of retinal progenitors in a sumoylation-dependent manner. Overexpression of ubc9 and hmgb3 decreased expression of the cell-cycle inhibitor p27Xic1. Furthermore, progenitor proliferation is regulated, at least in part, by sumoylation of transcription factor Sp1. These results suggest a significant role of sumoylation for cell cycle regulation in retinal progenitors.