PloS one, 2015-06, Vol.10 (6), p.e0130275-e0130275
2015
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- Autor(en) / Beteiligte
- Titel
- SUMOylation Blocks the Ubiquitin-Mediated Degradation of the Nephronophthisis Gene Product Glis2/NPHP7
- Ist Teil von
- PloS one, 2015-06, Vol.10 (6), p.e0130275-e0130275
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Glis2/NPHP7 is a transcriptional regulator mutated in type 7 nephronophthisis, an autosomal recessive ciliopathy associated with cystic and fibrotic kidney disease as well as characteristic extrarenal manifestations. While most ciliopathy-associated molecules are found in the cilium, Glis2/NPHP7 presumably localizes to the nucleus. However, the detection of endogenous Glis2/NPHP7 has remained unsuccessful, potentially due to its ubiquitylation-dependent rapid degradation. We report now that Glis2/NPHP7 is also SUMOylated, preferentially by PIAS4, which conjugates Glis2/NPHP7 to SUMO3. SUMOylation interferes with ubiquitylation and degradation of Glis2/NPHP7, suggesting that Glis2/NPHP7 protein levels are regulated by competing ubiquitylation/ SUMOylation. SUMOylation also alters the transcriptional activity of Glis2/NPHP7. While Glis2/NPHP7 activates the mouse insulin-2-promotor (mIns2), SUMOylated Glis2/NPHP7 lacks this property, and seems to act as a repressor. Taken together, our data reveal that Glis2/NPHP7 is extensively modified by post-translational modifications, suggesting that a tight control of this transcriptional regulator is required for normal development and tissue homeostasis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0130275Titel-ID: cdi_plos_journals_1689626227
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Binding Sites, Cloning, Degradation, Fibrosis, HEK293 Cells, Homeostasis, Humans, Immunoglobulins, Insulin, Kidney diseases, Kidney Diseases, Cystic - genetics, Kruppel-Like Transcription Factors - chemistry, Kruppel-Like Transcription Factors - genetics, Kruppel-Like Transcription Factors - metabolism, Localization, Medicine, Mice, Mutation, Nephronophthisis, Poly-ADP-Ribose Binding Proteins, Post-translation, Protein Inhibitors of Activated STAT - metabolism, Protein Stability, Proteins, Proteolysis, Signal transduction, SUMO protein, Sumoylation, Transcription, Transcription factors, Ubiquitin, Ubiquitin - metabolism, Ubiquitins - metabolism