Evidence map›Paper›PMID 23159736›Full record

ArticleMolecular cell2012

The auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway.

Konstantin I Piatkov, Luca Colnaghi, Miklos Békés, Alexander Varshavsky, Tony T Huang

Open access · greenAbstract read
In one paragraph

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 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Review
  5. N-degron pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Crystal structure of the Ate1 arginyl-tRNA-protein transferase and arginylation of N-degron substrates.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Recognition of nonproline N-terminal residues by the Pro/N-degron pathway.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Konstantin I PiatkovDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Luca Colnaghi
Miklos Békés
Alexander Varshavsky
Tony T Huang
New York University · USCalifornia Institute of Technology · US

Funding

The Functions, Mechanisms, and Regulation of N-Terminal ArginylationR01GM031530 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ALEXANDER J VARSHAVSKY · 1985 to 2026
$14.5M
Ubiquitin Ligases, Mechanisms and Functions of the N-End Rule PathwayR01DK039520 · NIDDK · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 1988 to 2025
$10.0M
MECHANICS AND FUNCTIONS OF THE N-END RULE PATHWAYR37DK039520 · NIDDK · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 1998 to 2007
$4.4M
Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility PathwayR01GM084244 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HUANG, TONY TUNG · 2009 to 2013
$2.3M
Ubiquitin Ligases, Mechanisms and Functions of the N-End Rule PathwayR56DK039520 · NIDDK · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI VARSHAVSKY, ALEXANDER J · 2008 to 2008
$161k
NIDDK NIH HHS DK039520NIDDK NIH HHS R01 DK039520NIDDK NIH HHS R37 DK039520NIDDK NIH HHS R56 DK039520NIGMS NIH HHS GM031530NIGMS NIH HHS GM084244NIGMS NIH HHS R01 GM031530NIGMS NIH HHS R01 GM084244
6 · The paper itself

Abstract

Deamidation of N-terminal Gln by the Ntaq1 Nt(Q)-amidase is a part of the Arg/N-end rule pathway, a ubiquitin-dependent proteolytic system. Here we identify Gln-Usp1(Ct), the C-terminal fragment of the autocleaved Usp1 deubiquitylase, as the first physiological Arg/N-end rule substrate that is targeted for degradation through deamidation of N-terminal Gln. Usp1 regulates genomic stability, in part through the deubiquitylation of monoubiquitylated PCNA, a DNA polymerase processivity factor. The autocleaved Usp1 remains a deubiquitylase because its fragments remain associated with Uaf1, an enhancer of Usp1 activity, until the Gln-Usp1(Ct) fragment is selectively destroyed by the Arg/N-end rule pathway. We also show that metabolic stabilization of Gln-Usp1(Ct) results in a decreased monoubiquitylation of PCNA and in a hypersensitivity of cells to ultraviolet irradiation. Thus, in addition to its other functions in DNA repair and chromosome segregation, the Arg/N-end rule pathway regulates genomic stability through the degradation-mediated control of the autocleaved Usp1 deubiquitylase.

Indexed as

Protein Processing, Post-TranslationalAmidohydrolasesAmino Acid MotifsAmino Acid SubstitutionAminoacyltransferasesAnimalsArabidopsis ProteinsCell LineEndopeptidasesEnzyme StabilityFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutAmidohydrolasesAminoacyltransferasesArabidopsis ProteinsarginyltransferaseEndopeptidasesNtaq1 protein, mousePeptide FragmentsProliferating Cell Nuclear AntigenUbiquitin-Specific ProteasesUSP1 protein, humanUsp1 protein, mouse

Identifiers

PMID23159736
PMCPMC3889152
OpenAlexW2100709246

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.