2. Academic Validation
  3. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis

IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis

  • Cell. 2007 Nov 16;131(4):669-81. doi: 10.1016/j.cell.2007.10.030.
Eugene Varfolomeev 1,  John W Blankenship,  Sarah M Wayson,  Anna V Fedorova,  Nobuhiko Kayagaki,  Parie Garg,  Kerry Zobel,  Jasmin N Dynek,  Linda O Elliott,  Heidi J A Wallweber,  John A Flygare,  Wayne J Fairbrother,  Kurt Deshayes,  Vishva M Dixit,  Domagoj Vucic
Affiliations

Affiliation

  • 1 Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080, USA.
PMID: 18022362 DOI: 10.1016/j.cell.2007.10.030
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.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-113534
    98.47%, IAP Antagonist