ArticlePloS one2012
HUWE1 and TRIP12 collaborate in degradation of ubiquitin-fusion proteins and misframed ubiquitin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- Deubiquitinases cleave ubiquitin-fused ribosomal proteins and physically counteract their targeting to the UFD pathway.Molecular cell · 2025Article
- Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12.Cell reports · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.Life science alliance · 2024Article
- Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae.Nature communications · 2023Article
- IL-1β turnover by the UBE2L3 ubiquitin conjugating enzyme and HECT E3 ligases limits inflammation.Nature communications · 2023Article
- HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways.Cell reports · 2023Article
- C16orf72/HAPSTR1 is a molecular rheostat in an integrated network of stress response pathways.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Up-regulation of ubiquitin-proteasome activity upon loss of NatA-dependent N-terminal acetylation.Life science alliance · 2022Article
- Proteasomal degradation of the tumour suppressor FBW7 requires branched ubiquitylation by TRIP12.Nature communications · 2021Article
- Fragmentation of Small-Cell Lung Cancer Regulatory States in Heterotypic Microenvironments.Cancer research · 2021Article
- The Dose-Dependent Pleiotropic Effects of the UBBFrontiers in molecular biosciences · 2021Review
- E3 Ubiquitin Ligase TRIP12: Regulation, Structure, and Physiopathological Functions.International journal of molecular sciences · 2020Review
- The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.Oncogene · 2020Article
- Reporter-Based Screens for the Ubiquitin/Proteasome System.Frontiers in chemistry · 2020Review
- Activity-Based Probes for HECT E3 Ubiquitin Ligases.Chembiochem : a European journal of chemical biology · 2017Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotic cells an uncleavable ubiquitin moiety conjugated to the N-terminus of a protein signals the degradation of the fusion protein via the proteasome-dependent ubiquitin fusion degradation (UFD) pathway. In yeast the molecular mechanism of the UFD pathway has been well characterized. Recently the human E3 ubiquitin-protein ligase TRIP12 was connected with the UFD pathway, but little is otherwise known about this system in mammalian cells. In the present work, we utilized high-throughput imaging on cells transfected with a targeted siRNA library to identify components involved in degradation of the UFD substrate Ub(G76V)-YFP. The most significant hits from the screen were the E3 ubiquitin-protein ligase HUWE1, as well as PSMD7 and PSMD14 that encode proteasome subunits. Accordingly, knock down of HUWE1 led to an increase in the steady state level and a retarded degradation of the UFD substrate. Knock down of HUWE1 also led to a stabilization of the physiological UFD substrate UBB(+1). Precipitation experiments revealed that HUWE1 is associated with both the Ub(G76V)-YFP substrate and the 26S proteasome, indicating that it functions late in the UFD pathway. Double knock down of HUWE1 and TRIP12 resulted in an additive stabilization of the substrate, suggesting that HUWE1 and TRIP12 function in parallel during UFD. However, even when both HUWE1 and TRIP12 are downregulated, ubiquitylation of the UFD substrate was still apparent, revealing functional redundancy between HUWE1, TRIP12 and yet other ubiquitin-protein ligases.
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