Cited by 2,372Cell death mechanisms and regulationCancer-related Molecular PathwaysUbiquitin and proteasome pathways

Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins

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Verhagen, Anne M, Ekert, Paul G, Pakusch, Miha, Silke, John, Connolly, Lisa M, Reid, Gavin E, Moritz, Robert L, Simpson, Richard J +1 more·2000·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(00)00009-x

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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”
  • 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].”

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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
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
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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