Evidence map›Paper›PMID 9482724›Full record

ArticleThe EMBO journal1998

Alphaviruses induce apoptosis in Bcl-2-overexpressing cells: evidence for a caspase-mediated, proteolytic inactivation of Bcl-2.

D Grandgirard, E Studer, L Monney, T Belser, I Fellay, C Borner, M R Michel

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

49 citing papers in PubMed, 186 citations in OpenAlex.

  1. Article
  2. Article
  3. Inhibition of induced-hepatic cancerFrontiers in oncology · 2022
    Article
  4. Article
  5. Review
  6. Article
  7. Genetic alterations and their clinical implications in DLBCL.Nature reviews. Clinical oncology · 2019
    Review
  8. Article
  9. Review
  10. Article
  11. RRM2 regulates Bcl-2 in head and neck and lung cancers: a potential target for cancer therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013
    Article
  12. Article
  13. Article
  14. Article
  15. The antitumor activity of the fungicide ciclopirox.International journal of cancer · 2010
    Article
  16. Article
  17. Review
  18. Intrinsically disordered proteins in bcl-2 regulated apoptosis.International journal of molecular sciences · 2010
    Review
  19. FKBP38 protects Bcl-2 from caspase-dependent degradation.The Journal of biological chemistry · 2010
    Article
  20. 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

7 authors at 1 institution in 1 country.

D GrandgirardInstitute of Medical Microbiology, University of Berne, Friedbuehlstrasse 51, CH-3010 Berne, Switzerland.
E Studer
L Monney
T Belser
I Fellay
C Borner
M R Michel
University of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced apoptosis. This might be achieved by preventing virus-induced activation of caspase-3, an IL-1beta-converting enzyme (ICE)-like cysteine protease that has been implicated in the death effector phase of apoptosis. Contrary to this model, we show that three cell types highly overexpressing functional Bcl-2 displayed caspase-3 activation and underwent apoptosis in response to infection with alphaviruses Semliki Forest and Sindbis as efficiently as vector control counterparts. In all three cell types, overexpressed 26 kDa Bcl-2 was cleaved into a 23 kDa protein. Antibody epitope mapping revealed that cleavage occurred at one or two target sites for caspases within the amino acid region YEWD31 (downward arrow) AGD34 (downward arrow) A, removing the N-terminal BH4 region known to be essential for the death-protective activity of Bcl-2. Preincubation of cells with the caspase inhibitor Z-VAD prevented Bcl-2 cleavage and partially restored the protective activity of Bcl-2 against virus-induced apoptosis. Moreover, a murine Bcl-2 mutant having Asp31, Asp34 and Asp36 substituted by Glu was resistant to proteolytic cleavage and abrogated apoptosis following virus infection. These findings indicate that alphaviruses can trigger a caspase-mediated inactivation of Bcl-2 in order to evade the death protection imposed by this survival factor.

Indexed as

CaspasesAmino Acid Chloromethyl KetonesAmino Acid SequenceAnimalsApoptosisbcl-2-Associated X ProteinCaspase 3Cell LineCysteine EndopeptidasesCysteine Proteinase InhibitorsEnzyme ActivationEpitopesFibroblastsGene ExpressionMiceMolecular Sequence DataAmino Acid Chloromethyl Ketonesbcl-2-Associated X Proteinbenzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketoneCasp3 protein, mouseCasp3 protein, ratCaspase 3CaspasesCysteine EndopeptidasesCysteine Proteinase InhibitorsEpitopesPoly(ADP-ribose) PolymerasesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2

Identifiers

PMID9482724
PMCPMC1170475
OpenAlexW2049295460

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.