Isabelle Carpentier

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Deregulated nuclear factor kappaB (NF-kappaB) activation plays an important role in inflammation and tumorigenesis. ABIN proteins have been characterized as negative regulators of NF-kappaB signaling. However, their mechanism of NF-kappaB inhibition remained unclear. With the help of a yeast two-hybrid screen, we identified ABIN proteins as novel(More)
Inappropriate functioning of the immune system is linked to immune deficiency, autoimmune disease, and cancer. It is therefore not surprising that intracellular immune signaling pathways are tightly controlled. One of the best studied transcription factors in immune signaling is NF-kappaB, which is activated by multiple receptors and regulates the(More)
The IkappaB kinases (IKKs) IKK-alpha and IKK-beta, and the IKK-related kinases TBK1 and IKK-epsilon, have essential roles in innate immunity through signal-induced activation of NF-kappaB, IRF3 and IRF7, respectively. Although the signaling events within these pathways have been extensively studied, the mechanisms of IKK and IKK-related complex assembly and(More)
ABINs have been described as three different proteins (ABIN-1, ABIN-2, ABIN-3) that bind the ubiquitin-editing nuclear factor-kappaB (NF-kappaB) inhibitor protein A20 and which show limited sequence homology. Overexpression of ABINs inhibits NF-kappaB activation by tumor necrosis factor (TNF) and several other stimuli. Similar to A20, ABIN-1 and ABIN-3(More)
We previously demonstrated that p38 MAPK is a crucial mediator in the NF-kappaB-dependent gene activation induced by TNF. Here, we have studied the role of several TNF receptor-associated proteins and caspases in p38 MAPK activation by TNF. The latter appears to be dependent on TRAF2, but independent of FADD or caspases. Remarkably, p38 MAPK activation by(More)
We have previously shown that lithium salts can considerably increase the direct cytotoxic effect of tumor necrosis factor (TNF) on various tumor cells in vitro and in vivo. However, the underlying mechanism has remained largely unknown. Here we show that the TNF-sensitizing effect of lithium chloride (LiCl) is independent of the type of cell death, either(More)
Linear polyubiquitination of proteins has recently been implicated in NF-κB signalling and is mediated by the linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP and Sharpin. However, the mechanisms that regulate linear ubiquitination are still unknown. Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF(More)
TNF is a multifunctional cytokine that plays a key role in innate immunity by inducing the expression of a variety of genes that are involved in an inflammatory response. TNF-induced NF-κB activation is one of the best studied signaling pathways in mammalian cells and has recently led to a revival of research in the biology of ubiquitin. Many NF-κB(More)
A20 (also known as TNFAIP3) is a cytoplasmic protein that plays a key role in the negative regulation of inflammation and immunity. Polymorphisms in the A20 gene locus have been identified as risk alleles for multiple human autoimmune diseases, and A20 has also been proposed to function as a tumor suppressor in several human B-cell lymphomas. A20 expression(More)
Collagen-induced arthritis (CIA) in mice is accompanied by splenomegaly due to the selective expansion of immature CD11b+ myeloblasts. Both disease manifestations are more pronounced in interferon-gamma receptor knock-out (IFN-gammaR KO) mice. We have taken advantage of this difference to test the hypothesis that the expanding CD11b+ splenic cell population(More)