Evidence map›Paper›PMID 29875129›Full record

ArticleThe EMBO journal2018

Dimer-specific immunoprecipitation of active caspase-2 identifies TRAF proteins as novel activators.

Alexander C Robeson, Kelly R Lindblom, Jeffrey Wojton, Sally Kornbluth, Kenkyo Matsuura

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Comparison of Target Recognition by TRAF1 and TRAF2.International journal of molecular sciences · 2020
    Article
  14. Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond.Frontiers in cell and developmental biology · 2020
    Review
  15. Roles of TRAFs in Ischemia-Reperfusion Injury.Frontiers in cell and developmental biology · 2020
    Review
  16. Article
  17. Article
  18. Article
  19. A Conserved Requirement forFrontiers in physiology · 2019
    Article
  20. 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

5 authors at 1 institution in 1 country.

Alexander C RobesonDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Kelly R LindblomDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Jeffrey WojtonDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
Sally KornbluthDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA sally.kornbluth@duke.edu kenkyo.matsuura@duke.edu.
Kenkyo MatsuuraDepartment of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA sally.kornbluth@duke.edu kenkyo.matsuura@duke.edu.ORCID 0000-0003-4612-6031
Duke Medical Center · US

Funding

ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
Control of caspase activation in apoptosisR01GM080333 · NIGMS · DUKE UNIVERSITY · PI KORNBLUTH, SALLY A · 2007 to 2015
$2.6M
Duke-UNC Chapel Hill Immunotherapy Training GrantT32CA211056 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHAO, NELSON J., SERODY, JONATHAN S. · 2017 to 2021
$2.2M
Regulation of REDD1 and caspase-2 by FASN inhibition in ovarian cancerF31CA183463 · NCI · DUKE UNIVERSITY · PI LINDBLOM, KELLY R. · 2014 to 2015
$37k
NCI NIH HHS F31 CA183463NCI NIH HHS T32 CA211056NIGMS NIH HHS R01 GM080333NIGMS NIH HHS T32 GM007184
6 · The paper itself

Abstract

Caspase-2 has been shown to initiate apoptotic cell death in response to specific intracellular stressors such as DNA damage. However, the molecular mechanisms immediately upstream of its activation are still poorly understood. We combined a caspase-2 bimolecular fluorescence complementation (BiFC) system with fluorophore-specific immunoprecipitation to isolate and study the active caspase-2 dimer and its interactome. Using this technique, we found that tumor necrosis factor receptor-associated factor 2 (TRAF2), as well as TRAF1 and 3, directly binds to the active caspase-2 dimer. TRAF2 in particular is necessary for caspase-2 activation in response to apoptotic cell death stimuli. Furthermore, we found that dimerized caspase-2 is ubiquitylated in a TRAF2-dependent manner at K15, K152, and K153, which in turn stabilizes the active caspase-2 dimer complex, promotes its association with an insoluble cellular fraction, and enhances its activity to fully commit the cell to apoptosis. Together, these data indicate that TRAF2 positively regulates caspase-2 activation and consequent cell death by driving its activation through dimer-stabilizing ubiquitylation.

Indexed as

Adaptor Proteins, Signal TransducingCaspase 2Cell LineHumansImmunoprecipitationProtein BindingProtein Interaction MappingProtein MultimerizationTNF Receptor-Associated Factor 1TNF Receptor-Associated Factor 3Adaptor Proteins, Signal TransducingCaspase 2TIFA protein, humanTNF Receptor-Associated Factor 1TNF Receptor-Associated Factor 3TRAF3 protein, humanapoptosisCaspase‐2dimer purificationTRAFubiquitylation

Identifiers

PMID29875129
PMCPMC6043850
OpenAlexW2805450045

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.