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 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.
Terada
Koji
K
Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Furukawa
Takahisa
T
D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D019070:Cell Lineage; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D016384:Consensus Sequence / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D025765:HMGB3 Protein / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025765:HMGB3 Protein; D012333:RNA, Messenger; D025841:Small Ubiquitin-Related Modifier Proteins; D016329:Sp1 Transcription Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D008239:Lysine