Evidence map›Paper›PMID 22701671›Full record

ArticlePloS one2012

Two nuclear localization signals in USP1 mediate nuclear import of the USP1/UAF1 complex.

Iraia Garcia-Santisteban, Kerman Zorroza, Jose Antonio Rodriguez

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
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  3. Review
  4. Article
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  6. Review
  7. Regulation of Deubiquitinating Enzymes by Post-Translational Modifications.International journal of molecular sciences · 2020
    Review
  8. Article
  9. Article
  10. Decision for cell fate: deubiquitinating enzymes in cell cycle checkpoint.Cellular and molecular life sciences : CMLS · 2016
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. The N-terminal 33 amino acid domain of Siva-1 is sufficient for nuclear localization.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2013
    Article
  16. Review
  17. 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

3 authors at 2 institutions in 1 country.

Iraia Garcia-SantistebanDepartment of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Spain.
Kerman Zorroza
Jose Antonio Rodriguez
University of the Basque Country · ESBioef - Fundación Vasca de Innovación e Investigación Sanitarias · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human deubiquitinase USP1 plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells. USP1 deubiquitinase activity is critically regulated by its interaction with the WD40 repeat-containing protein UAF1. Inhibiting the function of the USP1/UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target. Intriguingly, whereas UAF1 has been reported to locate in the cytoplasm, USP1 is a nuclear protein, although the sequence motifs that mediate its nuclear import have not been functionally characterized. Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex. Using a cellular relocation assay based on these results, we map the UAF1-binding site to a highly conserved 100 amino acid motif in USP1. Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs. Importantly, our findings have practical implications for the development of USP1-directed therapies. First, the UAF1-interacting region of USP1 identified here might be targeted to disrupt the USP1/UAF1 interaction with therapeutic purposes. On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1/UAF1 complex.

Indexed as

Active Transport, Cell NucleusAmino Acid SequenceArabidopsis ProteinsBinding SitesCloning, MolecularComputational BiologyEndopeptidasesFluorescent Antibody TechniqueHumansImmunoblottingImmunoprecipitationMicroscopy, ConfocalMolecular Sequence DataMultiprotein ComplexesMutagenesis, Site-DirectedNuclear Localization SignalsArabidopsis ProteinsEndopeptidasesMultiprotein ComplexesNuclear Localization SignalsNuclear ProteinsUbiquitin-Specific ProteasesUSP1 protein, humanWDR48 protein, human

Identifiers

PMID22701671
PMCPMC3368879
OpenAlexW2023431413

What OpenQuestion holds

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LicenceCC BY
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.