Evidence map›Paper›PMID 25774600›Full record

ArticleeLife2015

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases.

Ruming Chen, Cláudia Rato, Yahui Yan, Ana Crespillo-Casado, Hanna J Clarke, Heather P Harding, Stefan J Marciniak, Randy J Read, David Ron

Abstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
–field-weighted citation impact
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

57 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Regulation and outcomes of localized RNA translation.Wiley interdisciplinary reviews. RNA · 2022
    Review
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

9 authors.

Ruming ChenCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Cláudia RatoCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Yahui YanCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Ana Crespillo-CasadoCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Hanna J ClarkeCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Heather P HardingCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Stefan J MarciniakCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0001-8472-7183
Randy J ReadCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0001-8273-0047
David RonCambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.ORCID http://orcid.org/0000-0002-3014-5636

Funding

Medical Research Council G0601840Medical Research Council G1002610Wellcome Trust 082961Wellcome Trust 082961/Z/07/ZWellcome Trust 084812Wellcome Trust 084812/Z/08/ZWellcome Trust 100140
6 · The paper itself

Abstract

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex.

Indexed as

ActinsAmino Acid SequenceAnimalsCatalytic DomainCattleCHO CellsConserved SequenceCricetinaeCricetulusEukaryotic Initiation Factor-2HumansMiceModels, MolecularMolecular Sequence DataMutationPhosphorylationActinsEukaryotic Initiation Factor-2Ppp1r15a protein, mouseProtein Phosphatase 1biochemistrybiophysicscell linesE. colihumanmouserabbitstructural biology

Identifiers

PMID25774600
PMCPMC4394352

What OpenQuestion holds

Textmetadata
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.