Evidence map›Paper›PMID 21364655›Full record

ArticleCell death & disease2010

XIAP impairs Smac release from the mitochondria during apoptosis.

L Flanagan, J Sebastià, L P Tuffy, A Spring, A Lichawska, M Devocelle, J H M Prehn, M Rehm

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development.Apoptosis : an international journal on programmed cell death · 2025
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Anastasis: recovery from the brink of cell death.Royal Society open science · 2018
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  19. 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

8 authors at 1 institution in 1 country.

L FlanaganDepartment of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
J Sebastià
L P Tuffy
A Spring
A Lichawska
M Devocelle
J H M Prehn
M Rehm
Royal College of Surgeons in Ireland · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases 3, 7 and 9, and mitochondrial Smac (second mitochondria-derived activator of caspase) release during apoptosis inhibits the activity of XIAP. In this study we show that cytosolic XIAP also feeds back to mitochondria to impair Smac release. We constructed a fluorescent XIAP-fusion protein by labelling NH(2)- and COOH-termini with Cerulean fluorescent protein (C-XIAP-C). Immunoprecipitation confirmed that C-XIAP-C retained the ability to interact with Smac and impaired extrinsically and intrinsically activated apoptosis in response to tumour necrosis factor-related apoptosis-inducing ligand/cycloheximide and staurosporine. In C-XIAP-C-expressing cells, cytochrome c release from mitochondria proceeded normally, whereas Smac release was significantly prolonged and incomplete. In addition, physiological expression of native XIAP prolonged or limited Smac release in HCT-116 colon cancer cells and primary mouse cortical neurons. The Smac-binding capacity of XIAP, but not caspase inhibition, was central for mitochondrial Smac retention, as evidenced in experiments using XIAP mutants that cannot bind to Smac or effector caspases. Similarly, the release of a Smac mutant that cannot bind to XIAP was not impaired by C-XIAP-C expression. Full Smac release could however be provoked by rapid cytosolic C-XIAP-C depletion upon digitonin-induced plasma membrane permeabilization. Our findings suggest that although mitochondria may already contain pores sufficient for cytochrome c release, elevated amounts of XIAP can selectively impair and limit the release of Smac.

Indexed as

ApoptosisAnimalsApoptosis Regulatory ProteinsCarrier ProteinsCell Membrane PermeabilityCell ProliferationCells, CulturedCytochromes cDigitoninHumansLuminescent ProteinsMiceMitochondriaMitochondrial ProteinsNeuronsRecombinant Fusion ProteinsApoptosis Regulatory ProteinsCarrier ProteinsCytochromes cDiablo protein, mouseDigitoninLuminescent ProteinsMitochondrial ProteinsRecombinant Fusion ProteinsX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID21364655
PMCPMC3032314
OpenAlexW1996802358

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.