ArticleProceedings of the National Academy of Sciences of the United States of America2018
K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.
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Who cites it
175 citing papers in PubMed, 285 citations in OpenAlex.
- TRIM36 catalyzes K63-linked ubiquitination of TAK1 to drive septic inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2.Disease models & mechanisms · 2026Article
- Nogo-B attenuates vascular calcification by activating NRF2-SLC7A11 to enhance antioxidant defense.Redox biology · 2026Article
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Conformational landscapes resolved by ion mobility mass spectrometry reveal mechanisms of polyubiquitin-controlled phase separation.Chemical science · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Rv1983 promotes mycobacterial dissemination by triggering ferroptosis through GPX4 ubiquitination.Cellular & molecular biology letters · 2026Article
- Molecular architecture of meiotic pro-crossover factor HEI10 reveals coupling of higher-order assembly and ubiquitin chain formation.bioRxiv : the preprint server for biology · 2026Article
- Promoter Hypermethylation-Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5-Mediated Wnt/β-Catenin Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Artesunate Ameliorates APAP-induced Liver Injury by Promoting NEDD4L-Mediated Ubiquitination and Degradation of TXNIP.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- K63-linked ubiquitylation of S2P-RNAPII regulates transcription in a DNAPK inter-dependent manner in response to double-strand breaks.Nucleic acids research · 2026Article
- ARHGAP21 enhances metastasis in hepatocellular carcinoma by inhibiting ubiquitination of filamin A.Cell death discovery · 2026Article
- Casein kinase 2-mediated phosphorylation of the splicing factor SF3B3 plays a key role in esophageal squamous cell carcinoma progression.PLoS biology · 2026Article
- Cyclophilin A stabilizes the capsid protein p72 to facilitate African swine fever virus replication.Nature communications · 2026Article
- RNF90 promotes hepatic steatosis by degrading CPT1α to suppress fatty acid oxidation.The Journal of biological chemistry · 2026Article
- The Mechanism of Histone Ubiquitylation by the ASB9-CUL5 Ubiquitin Ligase.Molecular & cellular proteomics : MCP · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance.Frontiers in immunology · 2026Review
- Molecular dynamics simulations for understanding dual ubiquitination mechanisms to consider S-phase kinase-associated protein 2 (SKP2) as a potential drug target in breast cancer.Frontiers in chemistry · 2026Article
115 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Different polyubiquitin chain linkages direct substrates toward distinct cellular pathways. K63-linked ubiquitylation is known to regulate proteasome-independent events such as signal transduction, but its function in the context of heterogeneous ubiquitin chains remains unclear. Here, we report that K63 ubiquitylation plays a critical role in proteasome-mediated substrate degradation by serving as a "seed" for K48/K63 branched ubiquitin chains. Quantitative analysis revealed that K48/K63 branched linkages preferentially associate with proteasomes in cells. We found that ITCH-dependent K63 ubiquitylation of the proapoptotic regulator TXNIP triggered subsequent assembly of K48/K63 branched chains by recruiting ubiquitin-interacting ligases such as UBR5, leading to TXNIP degradation. These results reveal a role for K63 chains as a substrate-specific mark for proteasomal degradation involved in regulating cell fate. Our findings provide insight into how cellular interpretation of the ubiquitin code is altered by combinations of ubiquitin linkages.
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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.