The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Requirement of Both the Second and Third BIR Domains for the Relief of X-linked Inhibitor of Apoptosis Protein (XIAP)-mediated Caspase Inhibition by Smac
Open accessAbstract
The inhibitor of apoptosis proteins (IAP) are endogenous caspase inhibitors in the metazoan and characterized by the presence of baculoviral IAP repeats (BIR). X-linked IAP (XIAP) contains three BIR domains and directly inhibits effector caspases such as caspase-7 via a linker_BIR2 fragment and initiator caspases such as caspase-9 via the BIR3 domain. A mitochondrial protein Smac/DIABLO, which is released during apoptosis, antagonizes XIAP-mediated caspase inhibition by interacting directly with XIAP. Here, using glutathione S-transferase pulldown and caspase activity assay, we show that Smac is ineffective in relieving either caspase-7 or caspase-9 inhibition by XIAP domain fragments. In addition, Smac forms a ternary complex with caspase-7 and linker_BIR2, suggesting that Smac/linker_BIR2 interaction does not sterically exclude linker_BIR2/caspase-7 interaction. However, Smac is effective in removing caspase-7 and caspase-9 inhibition by XIAP fragments containing both the BIR2 and BIR3 domains. Surface plasmon resonance measurements show that Smac interacts with the BIR2 or BIR3 domain in micromolar dissociation constants. On the other hand, Smac interacts with an XIAP construct containing both BIR2 and BIR3 domains in a subnanomolar dissociation constant by the simultaneous interaction of the Smac dimer with the BIR2 and BIR3 domains of a single XIAP molecule. This 2:1 Smac/XIAP interaction not only possesses enhanced affinity but also sterically excludes XIAP/caspase-7 interaction, demonstrating the requirement of both BIR2 and BIR3 domains for Smac to relieve XIAP-mediated caspase inhibition.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Upon release from mitochondria, the N-terminal amino acid alanine-valine-proline-isoeuceucine (AVPI) of Smac binds to the domain of XIAP, depriving XIAP of its ability to bind to caspase, thereby promoting apoptosis.458”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [458]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Apoptosis in the Pathogenesis and Treatment of Disease
Thompson, C. B. (1995) · Science · doi:10.1126/science.7878464 · Cited by 6,524
Du, C., Fang, M., Li, Y., Li, L., & Wang, X. (2000) · Cell · doi:10.1016/s0092-8674(00)00008-8 · Cited by 3,513
Proliferation, cell cycle and apoptosis in cancer
Evan, G. I., & Vousden, K. H. (2001) · Nature · doi:10.1038/35077213 · Cited by 3,417
(2001) · PubMed · Cited by 2,381
Verhagen, A. M., Ekert, P. G., Pakusch, M., Silke, J., Connolly, L. M., Reid, G. E., Moritz, R. L., Simpson, R. J., & Vaux, D. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00009-x · Cited by 2,372
X-linked IAP is a direct inhibitor of cell-death proteases
Deveraux, Q. L., Takahashi, R., Salvesen, G. S., & Reed, J. C. (1997) · Nature · doi:10.1038/40901 · Cited by 1,956
Mechanisms of Caspase Activation and Inhibition during Apoptosis
Shi, Y. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00482-3 · Cited by 1,850
IAP proteins: blocking the road to death's door
Salvesen, G. S., & Duckett, C. S. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm830 · Cited by 1,756
Caspase structure, proteolytic substrates, and function during apoptotic cell death
Nicholson, D. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400598 · Cited by 1,562
Green, D. R. (1998) · Cell · doi:10.1016/s0092-8674(00)81728-6 · Cited by 1,193
Research works printed but not linked: 2
- Wang, 2001, Genes Dev., 15, 2922
- Huang, 2001, Cell, 104, 781
Cited by
Sorted by citations
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy
Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312
Molecular mechanisms of caspase regulation during apoptosis
Riedl, S. J., & Shi, Y. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1496 · Cited by 1,933
Small molecules, big targets: drug discovery faces the protein–protein interaction challenge
Scott, D. E., Bayly, A. R., Abell, C., & Skidmore, J. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.29 · Cited by 1,137
Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality
Arkin, M. R., Tang, Y., & Wells, J. A. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.09.001 · Cited by 1,065
Metadata
- Authors
- Huang, Y., Rich, R. L., Myszka, D. G., & Wu, H.
- Affiliations
- Cornell University (US)
- University of Utah (US)
- Corresponding author
- Wu, Hao
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 278
- Issue
- 49
- Pages
- 49517-49522
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2160029849
- Cited by
- 152
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 10 · 2012: 4
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI50872)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- XIAP, Smac/DIABLO, caspase inhibition, caspase-7, caspase-9, effector caspases, initiator caspases, BIR3 domain, ternary complex, apoptosis, protein-protein interaction affinity
- MeSH terms
- Carrier Proteins, Humans, Protein Binding, Proteins, Dimerization, Caspases, Mitochondrial Proteins, Intracellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, X-Linked Inhibitor of Apoptosis Protein, Caspase Inhibitors
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
