Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Dev Biol. 2010 Nov 1;347(1):180-94. doi: 10.1016/j.ydbio.2010.08.023. Epub 2010 Aug 27.
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 p27(Xic1). 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.
精确控制祖细胞增殖对于正常发育至关重要。然而，控制发育过程中细胞周期退出的正确时机的分子机制还知之甚少。我们在这里表明，泛素结合酶 Ubc9 控制视网膜祖细胞的细胞周期退出。我们发现 Ubc9 在 Xenopus 胚胎的视网膜祖细胞和干细胞中高度表达。Ubc9 与 Xenopus hmgb3 物理和功能相关，hmgb3 对于视网膜细胞增殖是必需的，并且 Ubc9 和 hmgb3 的过表达以依赖 SUMO 化的方式抑制视网膜祖细胞的细胞周期退出。Ubc9 和 hmgb3 的过表达降低了细胞周期抑制剂 p27(Xic1)的表达。此外，祖细胞增殖至少部分受到转录因子 Sp1 的 SUMO 化的调节。这些结果表明 SUMO 化在视网膜祖细胞的细胞周期调控中具有重要作用。
