Cited by 458Ubiquitin and proteasome pathwaysHeat shock proteins researchProtein Degradation and Inhibitors

An unstructured initiation site is required for efficient proteasome-mediated degradation

Prakash, Sumit, Tian, Lin, Ratliff, Kevin S, Lehotzky, Rebecca E, Matouschek, Andreas·2004·Nature Structural & Molecular Biology

Abstract

The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins in the cytosol and nucleus. Proteins are targeted to the proteasome by the covalent attachment of polyubiquitin chains. The ubiquitin modification serves as the proteasome recognition element but by itself is not sufficient for efficient degradation of folded proteins. We report that proteolysis of tightly folded proteins is accelerated greatly when an unstructured region is attached to the substrate. The unstructured region serves as the initiation site for degradation and is hydrolyzed first, after which the rest of the protein is digested sequentially. These results identify the initiation site as a novel component of the targeting signal, which is required to engage the proteasome unfolding machinery efficiently. The proteasome degrades a substrate by first binding to its ubiquitin modification and then initiating unfolding at an unstructured region.

Integrity signals

Registry

Crossref · 10.1038/nsmb814

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • β-catenin proteins undergo proteasomal destruction, which is greatly accelerated by the presence of IDRs in addition to the bound ubiquitin signal.

    “Next, the β-catenin proteins undergo proteasomal destruction [259, 260], which is greatly accelerated by the presence of IDRs in addition to the bound ubiquitin signal [262].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Prakash, S., Tian, L., Ratliff, K. S., Lehotzky, R. E., & Matouschek, A.
Affiliations
Northwestern University (US)
Corresponding author
Matouschek, Andreas
Venue
Nature Structural & Molecular Biology
Published
2004-08-15
Volume
11
Issue
9
Pages
830-837
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2069494008
Cited by
458
References
56
Citations by year
2026: 19 · 2025: 17 · 2024: 14 · 2023: 14 · 2022: 15 · 2021: 33 · 2020: 26 · 2019: 22 · 2018: 13 · 2017: 24 · 2016: 23 · 2015: 19 · 2014: 15 · 2013: 26 · 2012: 17
FWCI
7.22
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM63004, R01GM063004)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
proteasome, protein degradation, unstructured regions, initiation sites, polyubiquitin chains, protein unfolding, ATP-dependent proteolysis, protein folding
MeSH terms
Adenosine Triphosphate, Animals, Bacillus, Binding Sites, Catalysis, Cell Nucleus, Cysteine Endopeptidases, Cytosol, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Hydrolysis, Models, Biological, Multienzyme Complexes, Endopeptidases, Promoter Regions, Genetic, Protein Binding, Rabbits, Temperature, Time Factors, Protein Structure, Tertiary, Protein Folding, Ubiquitin, Proteasome Endopeptidase Complex

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review