Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins
Open accessAbstract
To identify proteins that bind mammalian IAP homolog A (MIHA, also known as XIAP), we used coimmuno-precipitation and 2D immobilized pH gradient/SDS PAGE, followed by electrospray ionization tandem mass spectrometry. DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP. The N-terminally processed, IAP-interacting form of DIABLO is concentrated in membrane fractions in healthy cells but released into the MIHA-containing cytosolic fractions upon UV irradiation. As transfection of cells with DIABLO was able to counter the protection afforded by MIHA against UV irradiation, DIABLO may promote apoptosis by binding to IAPs and preventing them from inhibiting caspases.
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MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space, including cytochrome c (CYCS) and SMAC.
“MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space [40, 44, 156]. These mitochondrial proteins include (but are not limited to) cytochrome c, somatic (CYCS), which usually operates as an electron shuttle in the mitochondrial respiratory chain [157–160], and diablo IAP-binding mitochondrial protein (DIABLO; also known as”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [162]
Cytosolic SMAC precipitates apoptosis by associating with members of the inhibitor of apoptosis (IAP) protein family, including XIAP.
“Cytosolic SMAC precipitates apoptosis by associating with members of the inhibitor of apoptosis (IAP) protein family, including X-linked inhibitor of apoptosis (XIAP) [162, 163, 181].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [162]
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- Authors
- 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.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Vaux, David L
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 102
- Issue
- 1
- Pages
- 43-53
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2162653594
- Cited by
- 2,372
- References
- 34
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 31 · 2023: 31 · 2022: 37 · 2021: 45 · 2020: 39 · 2019: 42 · 2018: 47 · 2017: 45 · 2016: 65 · 2015: 59 · 2014: 64 · 2013: 87 · 2012: 68
- FWCI
- 75.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- 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
- Smac/DIABLO, IAP proteins, XIAP, apoptosis, caspase inhibition, protein-protein interaction, UV-induced apoptosis, mammalian proteins
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Transformed, Cloning, Molecular, Humans, Mammals, Molecular Sequence Data, Proteins, Subcellular Fractions, Viral Proteins, Cysteine Proteinase Inhibitors, Gene Expression, Apoptosis, Sequence Homology, Amino Acid, Nucleopolyhedroviruses, Mitochondrial Proteins, Intracellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, Inhibitor of Apoptosis Proteins, Mice, X-Linked Inhibitor of Apoptosis Protein
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