IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis
(2007) In Cell 131(4). p.669-669- Abstract
- Inhibitor of apoptosis (IAP) proteins are antiapoptotic regulators that block cell death in response to diverse stimuli. They are expressed at elevated levels in human malignancies and are attractive targets for the development of novel cancer therapeutics. Herein, we demonstrate that small-molecule IAP antagonists bind to select baculovirus IAP repeat (BIR) domains resulting in dramatic induction of auto-ubiquitination activity and rapid proteasomal degradation of c-IAPs. The IAP antagonists also induce cell death that is dependent on TNF signaling and de novo protein biosynthesis. Additionally, the c-IAP proteins were found to function as regulators of NF-kappaB signaling. Through their ubiquitin E3 ligase activities c-IAP1 and c-IAP2... (More)
- Inhibitor of apoptosis (IAP) proteins are antiapoptotic regulators that block cell death in response to diverse stimuli. They are expressed at elevated levels in human malignancies and are attractive targets for the development of novel cancer therapeutics. Herein, we demonstrate that small-molecule IAP antagonists bind to select baculovirus IAP repeat (BIR) domains resulting in dramatic induction of auto-ubiquitination activity and rapid proteasomal degradation of c-IAPs. The IAP antagonists also induce cell death that is dependent on TNF signaling and de novo protein biosynthesis. Additionally, the c-IAP proteins were found to function as regulators of NF-kappaB signaling. Through their ubiquitin E3 ligase activities c-IAP1 and c-IAP2 promote proteasomal degradation of NIK, the central ser/thr kinase in the noncanonical NF-kappaB pathway. (Less)
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https://lup.lub.lu.se/record/1143647
- author
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell
- volume
- 131
- issue
- 4
- pages
- 669 - 669
- publisher
- Cell Press
- external identifiers
-
- pmid:18022362
- scopus:36048999753
- ISSN
- 1097-4172
- DOI
- 10.1016/j.cell.2007.10.030
- language
- English
- LU publication?
- no
- id
- 4893f09c-e827-459b-ac41-4529d6b6fa9d (old id 1143647)
- date added to LUP
- 2016-04-01 11:57:20
- date last changed
- 2022-04-21 00:14:37
@article{4893f09c-e827-459b-ac41-4529d6b6fa9d,
abstract = {{Inhibitor of apoptosis (IAP) proteins are antiapoptotic regulators that block cell death in response to diverse stimuli. They are expressed at elevated levels in human malignancies and are attractive targets for the development of novel cancer therapeutics. Herein, we demonstrate that small-molecule IAP antagonists bind to select baculovirus IAP repeat (BIR) domains resulting in dramatic induction of auto-ubiquitination activity and rapid proteasomal degradation of c-IAPs. The IAP antagonists also induce cell death that is dependent on TNF signaling and de novo protein biosynthesis. Additionally, the c-IAP proteins were found to function as regulators of NF-kappaB signaling. Through their ubiquitin E3 ligase activities c-IAP1 and c-IAP2 promote proteasomal degradation of NIK, the central ser/thr kinase in the noncanonical NF-kappaB pathway.}},
author = {{Varfolomeev, Eugene and Blankenship, John W and Wayson, Sarah M and Fedorova, Anna V and Kayagaki, Nobuhiko and Garg, Parie and Zobel, Kerry and Dynek, Jasmin N and Elliott, Linda O and Wallweber, Heidi J A and Flygare, Johan and Fairbrother, Wayne J and Deshayes, Kurt and Dixit, V}},
issn = {{1097-4172}},
language = {{eng}},
number = {{4}},
pages = {{669--669}},
publisher = {{Cell Press}},
series = {{Cell}},
title = {{IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis}},
url = {{http://dx.doi.org/10.1016/j.cell.2007.10.030}},
doi = {{10.1016/j.cell.2007.10.030}},
volume = {{131}},
year = {{2007}},
}