ArticleProceedings of the National Academy of Sciences of the United States of America2020
Proteins containing ubiquitin-like (Ubl) domains not only bind to 26S proteasomes but also induce their activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
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- The FAM111A Gene: Genetic, Epigenetic, and Pharmacological Targets and Mechanistic Insights with Clinical Relevance.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- UBL7 is indispensable for spermiogenesis through protecting critical factors from excessive degradation by proteasomes.Nature communications · 2025Article
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- USP14 is crucial for proteostasis regulation and α-synuclein degradation in human SH-SY5Y dopaminergic cells.Heliyon · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- ISGylation and E3 ubiquitin ligases: an Atlantic salmon genetic perspective.Frontiers in immunology · 2025Article
- Rice A20/AN1 protein, OsSAP10, confers water-deficit stress tolerance via proteasome pathway and positive regulation of ABA signaling in Arabidopsis.Plant cell reports · 2024Article
- HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity.Cancer research communications · 2024Article
- Viable mutations of mouse midnolin suppress B cell malignancies.The Journal of experimental medicine · 2024Article
- Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons.Cell reports · 2024Article
- Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.International journal of biological sciences · 2024Article
- A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane ofLife science alliance · 2023Article
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- The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation.Science (New York, N.Y.) · 2023Article
- FAT10 and NUB1L cooperate to activate the 26S proteasome.Life science alliance · 2023Article
- E6AP AZUL interaction with UBQLN1/2 in cells, condensates, and an AlphaFold-NMR integrated structure.Structure (London, England : 1993) · 2023Article
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
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2 authors at 1 institution in 1 country.
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Abstract
During protein degradation by the ubiquitin-proteasome pathway, latent 26S proteasomes in the cytosol must assume an active form. Proteasomes are activated when ubiquitylated substrates bind to them and interact with the proteasome-bound deubiquitylase Usp14/Ubp6. The resulting increase in the proteasome's degradative activity was recently shown to be mediated by Usp14's ubiquitin-like (Ubl) domain, which, by itself, can trigger proteasome activation. Many other proteins with diverse cellular functions also contain Ubl domains and can associate with 26S proteasomes. We therefore tested if various Ubl-containing proteins that have important roles in protein homeostasis or disease also activate 26S proteasomes. All seven Ubl-containing proteins tested-the shuttling factors Rad23A, Rad23B, and Ddi2; the deubiquitylase Usp7, the ubiquitin ligase Parkin, the cochaperone Bag6, and the protein phosphatase UBLCP1-stimulated peptide hydrolysis two- to fivefold. Rather than enhancing already active proteasomes, Rad23B and its Ubl domain activated previously latent 26S particles. Also, Ubl-containing proteins (if present with an unfolded protein) increased proteasomal adenosine 5'-triphosphate (ATP) hydrolysis, the step which commits substrates to degradation. Surprisingly, some of these proteins also could stimulate peptide hydrolysis even when their Ubl domains were deleted. However, their Ubl domains were required for the increased ATPase activity. Thus, upon binding to proteasomes, Ubl-containing proteins not only deliver substrates (e.g., the shuttling factors) or provide additional enzymatic activities (e.g., Parkin) to proteasomes, but also increase their capacity for proteolysis.
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