ArticleCell discovery2016
The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for degradation.
Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- Disruption of the SAGA CORE triggers collateral degradation of KAT2A.Nature communications · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Turnover of missense mutant cytosolic proteins proceeds in the absence of major quality control E3 ligases.microPublication biology · 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
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- PEX1The Journal of biological chemistry · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.Molecular cell · 2025Article
- A nuclear protein quality control system for elimination of nucleolus-related inclusions.The EMBO journal · 2025Article
- Preserve or destroy: Orphan protein proteostasis and the heat shock response.The Journal of cell biology · 2024Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.Life science alliance · 2024Article
- HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation.eLife · 2023Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- Golgi stress induces SIRT2 to counteract Shigella infection via defatty-acylation.Nature communications · 2022Article
- 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
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In eukaryotes, many proteins function in multi-subunit complexes that require proper assembly. To maintain complex stoichiometry, cells use the endoplasmic reticulum-associated degradation system to degrade unassembled membrane subunits, but how unassembled soluble proteins are eliminated is undefined. Here we show that degradation of unassembled soluble proteins (referred to as unassembled soluble protein degradation, USPD) requires the ubiquitin selective chaperone p97, its co-factor nuclear protein localization protein 4 (Npl4), and the proteasome. At the ubiquitin ligase level, the previously identified protein quality control ligase UBR1 (ubiquitin protein ligase E3 component n-recognin 1) and the related enzymes only process a subset of unassembled soluble proteins. We identify the homologous to the E6-AP carboxyl terminus (homologous to the E6-AP carboxyl terminus) domain-containing protein HUWE1 as a ubiquitin ligase for substrates bearing unshielded, hydrophobic segments. We used a stable isotope labeling with amino acids-based proteomic approach to identify endogenous HUWE1 substrates. Interestingly, many HUWE1 substrates form multi-protein complexes that function in the nucleus although HUWE1 itself is cytoplasmically localized. Inhibition of nuclear entry enhances HUWE1-mediated ubiquitination and degradation, suggesting that USPD occurs primarily in the cytoplasm. Altogether, these findings establish a new branch of the cytosolic protein quality control network, which removes surplus polypeptides to control protein homeostasis and nuclear complex assembly.
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Registered trials
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.