ArticleMolecular cell2012
The direction of protein entry into the proteasome determines the variety of products and depends on the force needed to unfold its two termini.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Pulling and gripping: Proteasomal translocation pathway elements differentially contribute to substrate unfolding.Protein science : a publication of the Protein Society · 2026Article
- Proteasomal surveillance of exposed cysteines.bioRxiv : the preprint server for biology · 2026Article
- The local mechanostructural properties of protein cargoes regulate nucleocytoplasmic transport.Nature physics · 2026Article
- Substrate secondary structure is associated with proteasomal cleavage propensity.Frontiers in bioinformatics · 2026Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing.Nature communications · 2024Article
- Ubiquitin-independent proteasomal degradation driven by C-degron pathways.Molecular cell · 2023Article
- The cytosolic N-terminal region of heterologously-expressed transmembrane channel-like protein 1 (TMC1) can be cleaved in HEK293 cells.PloS one · 2023Article
- Vulnerability of HIF1α and HIF2α to damage by proteotoxic stressors.Toxicology and applied pharmacology · 2022Article
- SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases.Frontiers in molecular biosciences · 2022Review
- The 20S as a stand-alone proteasome in cells can degrade the ubiquitin tag.Nature communications · 2021Article
- PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.Nature communications · 2021Article
- Article
- Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages.International journal of molecular sciences · 2021Article
- Proteasome in action: substrate degradation by the 26S proteasome.Biochemical Society transactions · 2021Review
- Mechanistic basis for ubiquitin modulation of a protein energy landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Reduced IκB-α Protein Levels in Peripheral Blood Cells of Patients with Multiple Sclerosis-A Possible Cause of Constitutive NF-κB Activation.Journal of clinical medicine · 2020Article
- Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera.Scientific reports · 2019Article
- Polyamine biosynthesis in Xenopus laevis: the xlAZIN2/xlODC2 gene encodes a lysine/ornithine decarboxylase.PloS one · 2019Article
- Endoplasmic reticulum-associated degradation and disposal of misfolded GPI-anchored proteins in Trypanosoma brucei.Molecular biology of the cell · 2018Article
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Authors and funding
11 authors.
Funding
Abstract
Poorly structured domains in proteins enhance their susceptibility to proteasomal degradation. To learn whether the presence of such a domain near either end of a protein determines its direction of entry into the proteasome, directional translocation was enforced on several proteasome substrates. Using archaeal PAN-20S complexes, mammalian 26S proteasomes, and cultured cells, we identified proteins that are degraded exclusively from either the C or N terminus and some showing no directional preference. This property results from interactions of the substrate's termini with the regulatory ATPase and could be predicted based on the calculated relative stabilities of the N and C termini. Surprisingly, the direction of entry into the proteasome affected markedly the spectrum of peptides released and consequently influenced the efficiency of MHC class I presentation. Thus, easily unfolded termini are translocated first, and the direction of translocation influences the peptides generated and presented to the immune system.
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