ArticleCell reports2023
HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Opportunities in cancer gene therapy: inhibiting MDM2 and restoring p14ARF as a means to activate p53.Molecular and cellular biochemistry · 2026Review
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- CircLOC375190 Promotes Mitochondrial Dysfunction and Ferroptosis in Neurons after Stroke by Stabilizing HUWE1 Through Interaction-Induced Ubiquitination and Degradation of IGF2BP2.Applied biochemistry and biotechnology · 2026Article
- A multivalent adaptor mechanism drives the nuclear import of proteasomes.Nature communications · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 2026Article
- Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells.ACS chemical biology · 2025Article
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- S-adenosylmethionine metabolism buffering is regulated by a decrease in glycine N-methyltransferase via the nuclear ubiquitin-proteasome system.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.Molecular systems biology · 2024Article
- Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.Life science alliance · 2024Article
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
HUWE1 is a large, enigmatic HECT-domain ubiquitin ligase implicated in the regulation of diverse pathways, including DNA repair, apoptosis, and differentiation. How HUWE1 engages its structurally diverse substrates and how HUWE1 activity is regulated are unknown. Using unbiased quantitative proteomics, we find that HUWE1 targets substrates in a largely cell-type-specific manner. However, we identify C16orf72/HAPSTR1 as a robust HUWE1 substrate in multiple cell lines. Previously established physical and genetic interactions between HUWE1 and HAPSTR1 suggest that HAPSTR1 positively regulates HUWE1 function. Here, we show that HAPSTR1 is required for HUWE1 nuclear localization and nuclear substrate targeting. Nuclear HUWE1 is required for both cell proliferation and modulation of stress signaling pathways, including p53 and nuclear factor κB (NF-κB)-mediated signaling. Combined, our results define a role for HAPSTR1 in gating critical nuclear HUWE1 functions.
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