Evidence map›Paper›PMID 22872644›Full record

ArticleThe Journal of biological chemistry2012

Fibrils colocalize caspase-3 with procaspase-3 to foster maturation.

Julie A Zorn, Dennis W Wolan, Nicholas J Agard, James A Wells

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Extract ofEvidence-based complementary and alternative medicine : eCAM · 2019
    Article
  9. Allosteric Tuning of Caspase-7: A Fragment-Based Drug Discovery Approach.Angewandte Chemie (International ed. in English) · 2017
    Article
  10. Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  11. Article
  12. Activation of AMPK byEvidence-based complementary and alternative medicine : eCAM · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  17. Article
  18. Article
  19. An Aggregation Advisor for Ligand Discovery.Journal of medicinal chemistry · 2015
    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

4 authors at 1 institution in 1 country.

Julie A ZornDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
Dennis W Wolan
Nicholas J Agard
James A Wells
University of California, San Francisco · US

Funding

Direct Chemical Activators of CaspasesR01CA136779 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2009 to 2013
$1.5M
Activation of procaspases with small moleculesF32CA119641 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOLAN, DENNIS WILLIAM · 2006 to 2008
$151k
Global Analysis of Proteolysis in the Innate Immune ResponseF32AI077177 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGARD, NICHOLAS J. · 2008 to 2010
$143k
NCI NIH HHS F32 CA119641NCI NIH HHS F32 CA119641-03NCI NIH HHS R01 CA136779NIAID NIH HHS F32 AI077177
6 · The paper itself

Abstract

Most proteases are expressed as inactive precursors, or zymogens, that become activated by limited proteolysis. We previously identified a small molecule, termed 1541, that dramatically promotes the maturation of the zymogen, procaspase-3, to its mature form, caspase-3. Surprisingly, compound 1541 self-assembles into nanofibrils, and localization of procaspase-3 to the fibrils promotes activation. Here, we interrogate the biochemical mechanism of procaspase-3 activation on 1541 fibrils in addition to proteogenic amyloid-β(1-40) fibrils. In contrast to previous reports, we find no evidence that procaspase-3 alone is capable of self-activation, consistent with its fate-determining role in executing apoptosis. In fact, mature caspase-3 is >10(7)-fold more active than procaspase-3, making this proenzyme a remarkably inactive zymogen. However, we also show that fibril-induced colocalization of trace amounts of caspase-3 or other initiator proteases with procaspase-3 dramatically stimulates maturation of the proenzyme in vitro. Thus, similar to known cellular signaling complexes, these synthetic or natural fibrils can serve as platforms to concentrate procaspase-3 for trans-activation by upstream proteases.

Indexed as

ApoptosisAmyloid beta-PeptidesCaspase 3CatalysisDimerizationDrug Delivery SystemsEnzyme ActivationEnzyme PrecursorsHumansKineticsModels, BiologicalModels, ChemicalPeptide HydrolasesSignal TransductionTranscriptional ActivationAmyloid beta-PeptidesCaspase 3Enzyme PrecursorsPeptide Hydrolases

Identifiers

PMID22872644
PMCPMC3460474
OpenAlexW1978235810

What OpenQuestion holds

Textmetadata
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.