Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family
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Several of the inhibitor of apoptosis protein (IAP) family members regulate apoptosis in response to various cellular assaults. Some members are also involved in cell signalling, mitosis and targeting proteins to the ubiquitin-proteasome degradation machinery. The most intensively studied family member, X-linked IAP (XIAP), is a potent inhibitor of caspase activity; hence, it is generally assumed that direct caspase inhibition is an important conserved function of most members of the family. Biochemical and structural studies have precisely mapped the elements of XIAP required for caspase inhibition. Intriguingly, these elements are not conserved among IAPs. Here, we review current knowledge of the caspase-inhibitory potential of the human IAPs and show that XIAP is probably the only bona fide caspase inhibitor, suggesting that the other family members never gained the ability to directly inhibit caspase activity.
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XIAP is the only IAP protein family member that counteracts the apoptotic cascade by stably binding to and hence physically blocking caspases.
“XIAP is the only IAP protein family member that counteracts the apoptotic cascade by stably binding to and hence physically blocking caspases [184, 185].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [185]
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References 58 · Cited by 813
- Authors
- Eckelman, B. P., Salvesen, G. S., & Scott, F. L.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Scott, Fiona L
- Venue
- The EMBO Reports
- Published
- 2006-10-01
- Volume
- 7
- Issue
- 10
- Pages
- 988-994
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1618369
- OpenAlex
- W2123123035
- Cited by
- 813
- References
- 58
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 15 · 2023: 27 · 2022: 25 · 2021: 44 · 2020: 27 · 2019: 39 · 2018: 29 · 2017: 36 · 2016: 41 · 2015: 39 · 2014: 57 · 2013: 67 · 2012: 65
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG15402, R01AG015402)
- National Cancer Institute (T32CA077109, T32-CA77109)
- 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
- inhibitor of apoptosis proteins, XIAP, caspase inhibition, apoptosis regulation, ubiquitin-proteasome degradation, signal transduction, mitosis
- MeSH terms
- Amino Acid Sequence, Glutathione Transferase, Humans, Models, Biological, Models, Molecular, Molecular Sequence Data, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Genes, X-Linked, Inhibitor of Apoptosis Proteins, X-Linked Inhibitor of Apoptosis Protein, Caspase Inhibitors
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