Proceedings of the National Academy of Sciences · 2005 · 147 citations · 42 references
Endogenous X-linked IapApoptosisImmunologyCell DeathCellular Iap1Tumor BiologySignaling PathwayCell RegulationAutophagyRing-mediated RegulationProtein AbundanceCell SignalingProtein FunctionCell BiologyTumor MicroenvironmentCell SurvivalSignal TransductionX-linked IapTumor SuppressorSystems BiologyMedicine
Inhibitor of apoptosis (IAP) proteins, which bind to caspases via their baculoviral IAP repeat domains, also bear RING domains that enable them to promote ubiquitylation of themselves and other interacting proteins. Here we show that the RING domain of cIAP1 allows it to bind directly to the RING of X-linked IAP, causing its ubiquitylation and degradation by the proteasome, thus revealing a mechanism by which IAPs can regulate their abundance. Expression of a construct containing the RING of cellular IAP1 was able to deplete melanoma cells of endogenous X-linked IAP, promoted apoptosis, and also markedly reduced their clonogenicity when treated with cisplatin. Cross control of protein levels by RING domains may therefore enable their levels to be manipulated therapeutically.
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Twenty proteins containing a C-terminal SOCS box form five structural classes
Douglas J. Hilton, Rachael T. Richardson, Warren S. Alexander et al. · Proceedings of the National Academy of Sciences · 1998 · 743 citations
Protein Assembly, Biomolecular Structure Prediction, Structural Bioinformatics +25