0000000000393748
AUTHOR
Arthur Marivin
Les IAP au cœur de la signalisation NF-κB
The function of IAP has long been limited to an inhibition of apoptosis through their capacity to bind some caspases. Since the expression of these proteins is altered in some tumor samples, IAPs are targets for anticancer therapy and many small molecules have been designed for their capacity to inhibit IAP-caspase interaction. Unexpectedly, these molecules appeared to significantly affect NF-κB activation. In this review, we will discuss the central role of cIAP1, cIAP2 and XIAP in the regulation of NF-κB activating signaling pathways.
IAP et Rho : enfin connectées
231 m/s n° 3, vol. 30, mars 2014 DOI : 10.1051/medsci/20143003003 5. Apcher S, Millot G, Daskalogianni C, et al. Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway. Proc Natl Acad Sci USA 2013 ; 110 : 17951-6. 6. de Turris V, Nicholson P, Orozco RZ, et al. Cotranscriptional effect of a premature termination codon revealed by live-cell imaging. RNA 2011 ; 17 : 2094-107. 7. Iborra FJ, Jackson DA, Cook PR. Coupled transcription and translation within nuclei of mammalian cells. Science 2001 ; 293 : 1139-42. 8. David A, Dolan BP, Hickman HD, et al. Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol 201…
Cellular Inhibitor of Apoptosis Protein-1 (cIAP1) Can Regulate E2F1 Transcription Factor-mediated Control of Cyclin Transcription
International audience; The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-B signaling pathways in the cytoplasm. However, in some primary cells and tumor cell lines, cIAP1 is expressed in the nucleus, and its nuclear function remains poorly understood. Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters. This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins. Chromatin immunoprec…
cIAP1 regulates TNF-mediated cdc42 activation and filopodia formation
International audience; umour necrosis factor-α (TNF) is a cytokine endowed with multiple functions, depending on the cellular and environmental context. TNF receptor engagement induces the formation of a multimolecular complex including the TNFR-associated factor TRAF2, the receptor-interaction protein kinase RIP1 and the cellular inhibitor of apoptosis cIAP1, the latter being essential for NF-κB activation. Here, we show that cIAP1 also regulates TNF-induced actin cytoskeleton reorganization through a cdc42-dependent, NF-κB-independent pathway. Deletion of cIAP1 prevents TNF-induced filopodia and cdc42 activation. The expression of cIAP1 or its E3-ubiquitin ligase-defective mutant restore…
The Inhibitor of Apoptosis (IAPs) in Adaptive Response to Cellular Stress.
Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various “guardian molecules.” These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to…