ArticleHuman molecular genetics2016
The ubiquitin ligase Ubr4 controls stability of podocin/MEC-2 supercomplexes.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Functional characterization of podocyte-expressed THSD7A in experimental membranous nephropathy.JCI insight · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Tyrosyl-tRNA synthetase has a noncanonical function in actin bundling.Nature communications · 2023Article
- BIG Modulates Stem Cell Niche and Meristem Development via SCR/SHR Pathway in Arabidopsis Roots.International journal of molecular sciences · 2022Article
- UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.Nature communications · 2022Article
- Article
- Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging.Nature communications · 2021Article
- The tissue proteome in the multi-omic landscape of kidney disease.Nature reviews. Nephrology · 2021Review
- Recognition of nonproline N-terminal residues by the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis.Journal of the American Society of Nephrology : JASN · 2020Article
- MOLECULAR DESIGN OF THE KIDNEY FILTRATION BARRIER.Transactions of the American Clinical and Climatological Association · 2020Article
- Aberrant UBR4 expressions in Hirschsprung disease patients.BMC pediatrics · 2019Article
- Metabolic rewiring of the hypertensive kidney.Science signaling · 2019Article
- High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6.American journal of physiology. Renal physiology · 2019Article
- Gid10 as an alternative N-recognin of the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice.Cell reports · 2019Article
- The ubiquitin-proteasome system in kidney physiology and disease.Nature reviews. Nephrology · 2019Review
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
The PHB-domain protein podocin maintains the renal filtration barrier and its mutation is an important cause of hereditary nephrotic syndrome. Podocin and its Caenorhabditis elegans orthologue MEC-2 have emerged as key components of mechanosensitive membrane protein signalling complexes. Whereas podocin resides at a specialized cell junction at the podocyte slit diaphragm, MEC-2 is found in neurons required for touch sensitivity. Here, we show that the ubiquitin ligase Ubr4 is a key component of the podocin interactome purified both from cultured podocytes and native glomeruli. It colocalizes with podocin and regulates its stability. In C. elegans, this process is conserved. Here, Ubr4 is responsible for the degradation of mislocalized MEC-2 multimers. Ubiquitylomic analysis of mouse glomeruli revealed that podocin is ubiquitylated at two lysine residues. These sites were Ubr4-dependent and were conserved across species. Molecular dynamics simulations revealed that ubiquitylation of one site, K301, do not only target podocin/MEC-2 for proteasomal degradation, but may also affect stability and disassembly of the multimeric complex. We suggest that Ubr4 is a key regulator of podocyte foot process proteostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.