The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome
Abstract
Apoptosis is an evolutionarily conserved cell suicide process executed by cysteine proteases (caspases) and regulated by the opposing factions of the Bcl-2 protein family. Mammalian caspase-9 and its activator Apaf-1 were thought to be essential, because mice lacking either of them display neuronal hyperplasia and their lymphocytes and fibroblasts seem resistant to certain apoptotic stimuli. Because Apaf-1 requires cytochrome c to activate caspase-9, and Bcl-2 prevents mitochondrial cytochrome c release, Bcl-2 is widely believed to inhibit apoptosis by safeguarding mitochondrial membrane integrity. Our results suggest a different, broader role, because Bcl-2 overexpression increased lymphocyte numbers in mice and inhibited many apoptotic stimuli, but the absence of Apaf-1 or caspase-9 did not. Caspase activity was still discernible in cells lacking Apaf-1 or caspase-9, and a potent caspase antagonist both inhibited apoptosis and retarded cytochrome c release. We conclude that Bcl-2 regulates a caspase activation programme independently of the cytochrome c/Apaf-1/caspase-9 'apoptosome', which seems to amplify rather than initiate the caspase cascade.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Accordingly, blocking post-mitochondrial caspase activation by genetic means or with specific pharmacological inhibitors, such as to N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethylketone (Z-VAD-fmk) and (3S)-5-(2,6-difluorophenoxy)-3-[[(2S)-3-methyl-1-oxo-2-[(2-quinolinylcarbonyl)amino]butyl]amino]-4-oxo-pentanoic acid hydrate (Q-VD-OPh), generally delays (but does not prevent) intrinsic apopt”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [225]
Citations
Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
Hengartner, M. O. (2000) · Nature · doi:10.1038/35037710 · Cited by 5,779
The Bcl2 family: regulators of the cellular life-or-death switch
Cory, S., & Adams, J. M. (2002) · Nature Reviews Cancer · doi:10.1038/nrc883 · Cited by 4,032
Self-citationIdentification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., Lazebnik, Y. A., et al. (1995) · Nature · doi:10.1038/376037a0 · Cited by 3,980
Self-citationBCL-2 family members and the mitochondria in apoptosisPreprint
Gross, A., McDonnell, J. M., & Korsmeyer, S. J. (1999) · Genes & Development · doi:10.1101/gad.13.15.1899 · Cited by 3,642
A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998) · Nature · doi:10.1038/34112 · Cited by 3,239
(2001) · PubMed · Cited by 2,381
Liu, X., Zou, H., Slaughter, C. A., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80197-x · Cited by 1,835
Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
Kuida, K., Haydar, T. F., Kuan, C.-Y., Gu, Y., Taya, C., Karasuyama, H., Su, M. S.-S., Rakic, P., & Flavell, R. A. (1998) · Cell · doi:10.1016/s0092-8674(00)81476-2 · Cited by 1,643
Self-citationBouillet, P., Metcalf, D., Huang, D. C. S., Tarlinton, D. M., Kay, T. W. H., Köntgen, F., Adams, J. M., & Strasser, A. (1999) · Science · doi:10.1126/science.286.5445.1735 · Cited by 1,504
Self-citation
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationThe BCL-2 protein family: opposing activities that mediate cell death
Youle, R. J., & Strasser, A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2308 · Cited by 4,806
Self-citationDanial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
Singh, R., Letai, A., & Sarosiek, K. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0089-8 · Cited by 2,111
The Role of Mitochondria in Apoptosis
Wang, C., & Youle, R. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134850 · Cited by 1,987
Metadata
- Authors
- Marsden, V. S., O'Connor, L., O'Reilly, L. A., Silke, J., Metcalf, D., Ekert, P. G., Huang, D. C. S., Cecconi, F., Kuida, K., Tomaselli, K. J., Roy, S., Nicholson, D. W., Vaux, D. L., Bouillet, P., Adams, J. M., & Strasser, A.
- Affiliations
- Walter and Eliza Hall Institute of Medical Research (AU)
- University of Rome Tor Vergata (IT)
- Vertex Pharmaceuticals (United States) (US)
- Merck Canada Inc. (Canada) (CA)
- Corresponding author
- Strasser, Andreas
- ORCID
- Venue
- Nature
- Published
- 2002-09-25
- Volume
- 419
- Issue
- 6907
- Pages
- 634-637
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1978093163
- Cited by
- 578
- References
- 30
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 17 · 2023: 13 · 2022: 14 · 2021: 22 · 2020: 13 · 2019: 17 · 2018: 18 · 2017: 26 · 2016: 24 · 2015: 18 · 2014: 24 · 2013: 15 · 2012: 20
- FWCI
- 21.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Keywords
- apoptosis, Bcl-2, caspase activation, caspase-9, Apaf-1, cytochrome c release, apoptosome, Bcl-2 family proteins, lymphocyte proliferation, mitochondrial membrane integrity
- MeSH terms
- Animals, B-Lymphocytes, Cells, Cultured, Cytochrome c Group, Enzyme Activation, Hematopoiesis, Mice, Inbred C57BL, Proteins, T-Lymphocytes, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Caspases, Mice, Caspase 9, Apoptotic Protease-Activating Factor 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
