Research Topics
Genomes and Genes
| Daniela RotinSummaryAffiliation: The Hospital for Sick Children Country: Canada Publications
| Collaborators
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Detail Information
Publications
Neural stem cells from protein tyrosine phosphatase sigma knockout mice generate an altered neuronal phenotype in cultureDavid L Kirkham
Department of Pathology and Molecular Medicine, McMaster University, Hamilton Ontario, L8N 3Z5, Canada
BMC Neurosci 7:50. 2006....
Physiological functions of the HECT family of ubiquitin ligasesDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children, Ontario, Canada
Nat Rev Mol Cell Biol 10:398-409. 2009..The physiological functions of the yeast HECT E3 ligase Rsp5 are the best known, but the functions of HECT E3 enyzmes in metazoans are now becoming clearer from in vivo studies...- Role of the UPS in Liddle syndromeDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Ontario, M5G 1X8, Canada
BMC Biochem 9:S5. 2008..PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com)... 
ENaC and its regulatory proteins as drug targets for blood pressure controlDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children, TMDT MaRS, Rm 11 305, 101 College St, Toronto, Ont, Canada
Curr Drug Targets 9:709-16. 2008....- Role of the ubiquitin system in regulating ion transportDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children and Biochemistry Department, University of Toronto, Toronto, Canada
Pflugers Arch 461:1-21. 2011..We also briefly discuss the role of ubiquitin like molecules (such as SUMO) in such regulation, for which much less is known so far... - Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and functionAvinash Persaud
Programs in Cell Biology and Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
EMBO J 30:3259-73. 2011..These results identify Nedd4-1 as a key regulator of FGFR1 endocytosis and signalling during neuronal differentiation and embryonic development... - Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arraysAvinash Persaud
Programs in Cell Biology and Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada
Mol Syst Biol 5:333. 2009..g. FGFR), suggesting Nedd4-1 suppresses their signalling. These results demonstrate the feasibility of identifying substrates and deciphering substrate specificity of mammalian E3 ligases... - The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical poolChen Lu
Program in Cell Biology, The Hospital for Sick Children, Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
Traffic 8:1246-64. 2007..These results suggest that the ENaC PY motifs (and Nedd4-2) primarily regulate channel internalization but also affect cAMP-dependent replenishment, providing important insight into the Liddle syndrome defects... - Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domainM Christine Bruce
Program in Cell and Structure Biology, The Hospital for Sick Children, University of Toronto, 101 College Street, Toronto, ON, Canada, M5G 1L7
Biochem J 415:155-63. 2008..These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability... - Use of kinase inhibitors to correct ΔF508-CFTR functionAgata M Trzcinska-Daneluti
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1L7
Mol Cell Proteomics 11:745-57. 2012.... - Regulation of Commissureless by the ubiquitin ligase DNedd4 is required for neuromuscular synaptogenesis in Drosophila melanogasterBryant Ing
The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
Mol Cell Biol 27:481-96. 2007..These results demonstrate that dNedd4 and ubiquitination are required for Commissureless endocytosis and proper neuromuscular synaptogenesis... - Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitinationYoungshil Pak
Program in Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8
J Cell Biol 175:631-45. 2006..These results demonstrate a novel mechanism by which the ubiquitin-ligase Nedd4, via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination... - Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complexVoula Kanelis
Programme in Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Structure 14:543-53. 2006..In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development... - The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1Fatemeh Fouladkou
Program in Cell Biology and the Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada
J Biol Chem 285:6770-80. 2010..These results suggest that Nedd4-1 is a suppressor of Tsp1 and that increased levels of Tsp-1 in the Nedd4-1 knock-out mice may have contributed to the developmental defect observed in the embryos... - Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domainSilke Wiesner
Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
Cell 130:651-62. 2007..Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells... - Interactions between the three CIN85 SH3 domains and ubiquitin: implications for CIN85 ubiquitinationIrina Bezsonova
Department of Chemistry, University of Toronto, 80 St George Street, Toronto, ON, Canada M5S 1A8
Biochemistry 47:8937-49. 2008..These results suggest that competition between Cbl and ubiquitin binding to CIN85 regulates Cbl function and EGFR endocytosis... - A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteinsRuth Milkereit
Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto, Toronto, Ontario, Canada
PLoS ONE 6:e27478. 2011..While we had demonstrated earlier the requirement of the E3 ubiquitin ligase Nedd4 for LAPTM5 sorting to lysosomes, the regulation of sorting of LAPTM4 proteins is less clear... - A splice isoform of DNedd4, DNedd4-long, negatively regulates neuromuscular synaptogenesis and viability in DrosophilaYunan Zhong
Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
PLoS ONE 6:e27007. 2011..DNedd4 is an E3 ubiquitin ligase comprised of a C2-WW(x3)-Hect domain architecture, which includes several splice isoforms, the most prominent ones are dNedd4-short (dNedd4S) and dNedd4-long (dNedd4Lo)... - High-content functional screen to identify proteins that correct F508del-CFTR functionAgata M Trzcinska-Daneluti
Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario M5G 1L7, Canada
Mol Cell Proteomics 8:780-90. 2009..This assay can also be utilized for RNAi screens to identify inhibitory proteins that block correction of F508del-CFTR, small molecule, and peptide screens... - Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channelPauline C Henry
Programme in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
J Biol Chem 278:20019-28. 2003..Collectively, these results suggest that high affinity of WW domain-PY-motif interactions rather than affiliation with Nedd4-1/Nedd-2 is critical for ENaC suppression by Nedd4 proteins... - LAPTM5 protein is a positive regulator of proinflammatory signaling pathways in macrophagesWioletta K Glowacka
Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario M5G 1L7, Canada
J Biol Chem 287:27691-702. 2012..They also highlight a role for the endosomal/lysosomal system in regulating signaling via cytokine and pattern recognition receptors... - Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like diseaseToshihiro Kimura
Departments of Biochemistry and Physiology, The Hospital for Sick Children, Programs in Cell Biology and Neuroscience and Mental Health, and University of Toronto, Toronto, ON, Canada M5G 1X8
Proc Natl Acad Sci U S A 108:3216-21. 2011..Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia... - The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis and cell survival in melanoma cellsEva M Amsen
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
J Biol Chem 281:121-8. 2006..Collectively, these results suggest that CNrasGEF regulates melanogenesis but that it also has a distinct role in regulating cell proliferation/apoptosis... - Use of proteome arrays to globally identify substrates for E3 ubiquitin ligasesAvinash Persaud
Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada
Methods Mol Biol 759:215-24. 2011..The in vitro ubiquitylation and binding substrates identified in these screens can provide invaluable insight into the cellular pathways in which E3 ligases participate... - The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localizationFatemeh Fouladkou
Hospital for Sick Children and Biochemistry Department, University of Toronto, MaRS TMDT, 101 College Street, Toronto, Ontario M5G 1L7, Canada
Proc Natl Acad Sci U S A 105:8585-90. 2008..Taken together, our results fail to support a role for Nedd4-1 as the E3 ligase regulating PTEN stability and subcellular localization... - Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeastRonish Gupta
Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
Mol Syst Biol 3:116. 2007..The development of a platform for global discovery of E3 substrates is invaluable for understanding the cellular pathways in which they participate, and could be utilized for the identification of drug targets... - A strategy for modulation of enzymes in the ubiquitin systemAndreas Ernst
Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada
Science 339:590-5. 2013..Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system... - Functional rescue of DeltaF508-CFTR by peptides designed to mimic sorting motifsPatrick Kim Chiaw
Research Institute, Hospital for Sick Children, University of Toronto, ON, Canada
Chem Biol 16:520-30. 2009.... - The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in micePreena Nagpal
Keenan Research Centre of the LiKaShing Knowledge Institute, St Michaels Hospital, Toronto, Ontario, Canada
PLoS ONE 7:e46427. 2012..These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo... - Regulation of lipid droplet turnover by ubiquitin ligasesPhilipp Alberts
Cell Biology Program, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, Ontario, M5G 1L7, Canada
BMC Biol 8:94. 2010..A deficiency of spartin apparently causes lipid droplets to accumulate... - Protein-tyrosine phosphatase sigma is associated with ulcerative colitisAleixo M Muise
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, 555 University Ave, Toronto, Ontario, Canada
Curr Biol 17:1212-8. 2007..We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis... - Nedd4-2 and the regulation of epithelial sodium transportDaniela Rotin
Program in Cell Biology, The Hospital for Sick Children, Biochemistry Department, University of Toronto Toronto, ON, Canada
Front Physiol 3:212. 2012..Collectively, these new findings underscore the physiological importance of Nedd4-2 in regulating epithelial salt and fluid transport and balance... - N-cadherin is an in vivo substrate for protein tyrosine phosphatase sigma (PTPsigma) and participates in PTPsigma-mediated inhibition of axon growthRoberta Siu
Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8, Ontario, Canada
Mol Cell Biol 27:208-19. 2007..We conclude that N-cadherin is a physiological substrate for PTPsigma and that N-cadherin (and likely beta-catenin) participates in PTPsigma-mediated inhibition of axon growth... - Apical junction complex proteins and ulcerative colitis: a focus on the PTPRS geneAleixo Muise
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Program in Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
Expert Rev Mol Diagn 8:465-77. 2008..We will focus on the PTPRS (encoding PTPsigma) gene and discuss its and other apical junction complex proteins' role in the pathogenesis of UC... - Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activationYoungshil Pak
Program in Cell Biology, The Hospital for Sick Children, and Biochemistry Department, University of Toronto, Toronto, M5G 1X8 Ontario, Canada
Mol Cell Biol 22:7942-52. 2002..The present study provides the first demonstration of direct physical association between a Ras activator and a GPCR, leading to agonist-induced Ras activation.. - A high throughput screen to identify substrates for the ubiquitin ligase Rsp5Bart Kus
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
J Biol Chem 280:29470-8. 2005..The combination of this sensitive assay and the availability of purified substrates will enable the identification of substrates for any purified E3 enzyme... - The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptorAndrea Vecchione
Department of Urology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Mol Cell Biol 23:3363-72. 2003..This is the first demonstration of regulation of stability of a tyrosine kinase receptor by the Nedd4 (HECT) family of E3 ligases... - Regulation of the epithelial Na+ channel by cytosolic ATPToru Ishikawa
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060 0818, Japan
J Biol Chem 278:38276-86. 2003..We propose that this novel ATP regulation of ENaC may be, at least in part, involved in the fine-tuning of ENaC activity under physiologic and pathophysiologic conditions... - Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteinsJean Sebastien Rougier
Department of Pharmacology and Toxicology, Service of Cardiology, University of Lausanne, Rue du Bugnon 27, CH 1005 Lausanne, Switzerland
Am J Physiol Cell Physiol 288:C692-701. 2005..This study shows that Nedd4-dependent ubiquitination of Na(v) channels may represent a general mechanism regulating the excitability of neurons and myocytes via modulation of channel density at the plasma membrane... - Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptorAnna Myat
Molecular Neurobiology Group, MRC Centre for Developmental Neurobiology, King s College London, New Hunt s House, Guy s Campus, London SE1 1UL, United Kingdom
Neuron 35:447-59. 2002..Our results show that changes in axonal sensitivity to external cues during pathfinding across the midline makes use of ubiquitin-dependent mechanisms to regulate transmembrane protein levels...