ArticleProceedings of the National Academy of Sciences of the United States of America2010
Sumoylation activates the transcriptional activity of Pax-6, an important transcription factor for eye and brain development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 2026Article
- The Mammalian Ocular Lens in Focus: Development, Anatomy, Physiology, Transparency, Biomechanics, and Age-related Challenges.Journal of visualized experiments : JoVE · 2026Review
- Blockage of SUMO E1 enzyme inhibits ocular lens fibrosis by mediating SMAD4 SUMOylation.Genes & diseases · 2026Article
- The Dynamic Regulation of Daxx-Mediated Transcriptional Inhibition by SUMO and PML NBs.International journal of molecular sciences · 2025Review
- Multi-tissue transcriptome-wide association study identifies novel candidate susceptibility genes for cataract.Frontiers in ophthalmology · 2024Article
- SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.Aging · 2023Article
- HSP90β prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of SUMOylation on RNA metabolism in cancers.Frontiers in molecular biosciences · 2023Review
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Role of Post-translational Modification of Silent Mating Type Information Regulator 2 Homolog 1 in Cancer and Other Disorders.Journal of cancer prevention · 2022Review
- New insights into the mechanisms of age-related protein-protein crosslinking in the human lens.Experimental eye research · 2021Review
- Article
- SUMO and Transcriptional Regulation: The Lessons of Large-Scale Proteomic, Modifomic and Genomic Studies.Molecules (Basel, Switzerland) · 2021Review
- Editorial: Apoptosis and Senescence in Vertebrate Development.Frontiers in cell and developmental biology · 2021Article
- The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Epithelial Cells Through the Proapoptotic Regulator Bax.Frontiers in cell and developmental biology · 2021Article
- Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses.Aging cell · 2020Article
- PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury.Cell death & disease · 2020Article
- Article
- The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study.Cell transplantation · 2019Article
- A comprehensive spatial-temporal transcriptomic analysis of differentiating nascent mouse lens epithelial and fiber cells.Experimental eye research · 2018Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Pax-6 is an evolutionarily conserved transcription factor regulating brain and eye development. Four Pax-6 isoforms have been reported previously. Although the longer Pax-6 isoforms (p46 and p48) bear two DNA-binding domains, the paired domain (PD) and the homeodomain (HD), the shorter Pax-6 isoform p32 contains only the HD for DNA binding. Although a third domain, the proline-, serine- and threonine-enriched activation (PST) domain, in the C termini of all Pax-6 isoforms mediates their transcriptional modulation via phosphorylation, how p32 Pax-6 could regulate target genes remains to be elucidated. In the present study, we show that sumoylation at K91 is required for p32 Pax-6 to bind to a HD-specific site and regulate expression of target genes. First, in vitro-synthesized p32 Pax-6 alone cannot bind the P3 sequence, which contains the HD recognition site, unless it is preincubated with nuclear extracts precleared by anti-Pax-6 but not by anti-small ubiquitin-related modifier 1 (anti-SUMO1) antibody. Second, in vitro-synthesized p32 Pax-6 can be sumoylated by SUMO1, and the sumoylated p32 Pax-6 then can bind to the P3 sequence. Third, Pax-6 and SUMO1 are colocalized in the embryonic optic and lens vesicles and can be coimmunoprecipitated. Finally, SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm, and sumoylation significantly enhances the DNA-binding ability of p32 Pax-6 and positively regulates gene expression. Together, our results demonstrate that sumoylation activates p32 Pax-6 in both DNA-binding and transcriptional activities. In addition, our studies demonstrate that p32 and p46 Pax-6 possess differential DNA-binding and regulatory activities.
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