Elodie Lafont

Elodie Lafont
Université de Rennes 1 | UR1 · CLCC Eugène Marquis

PhD

About

46
Publications
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Introduction
Elodie Lafont currently works at the University Rennes 1, CLCC Eugène Marquis. She is interested in understanding the role of PTMs in the modulation of immune receptor signalling.

Publications

Publications (46)
Article
Full-text available
The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ubiquitin ligase which catalyses the generation of linear ubiquitin linkages de novo LUBAC is a crucial component of various immune receptor signalling pathways. Here, we show that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced...
Article
Full-text available
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-...
Article
Full-text available
The linear-ubiquitin chain assembly complex (LUBAC) modulates signalling via various immune receptors. In tumour necrosis factor (TNF) signalling, linear (also known as M1) ubiquitin enables full gene activation and prevents cell death. However, the mechanisms underlying cell death prevention remain ill-defined. Here, we show that LUBAC activity en...
Article
Full-text available
Throughout tumour progression, tumour cells are exposed to various intense cellular stress conditions owing to intrinsic and extrinsic cues, to which some cells are remarkably able to adapt. Death Receptor (DR) signalling and the Unfolded Protein Response (UPR) are two stress responses that both regulate a plethora of outcomes, ranging from prolife...
Preprint
Full-text available
Unfolded Protein Response (UPR) and Death Receptor (DR) signalling are cellular stress pathways frequently activated towards pro-tumoral cellular outputs in cancer. Experimental evidence has highlighted functional links between the UPR and signalling by the DR TRAIL-R1/2. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of th...
Article
Full-text available
Cell death plays a pivotal role in the maintenance of tissue homeostasis. Key players in the controlled induction of cell death are the Death Receptors (DR). CD95 is a prototypic DR activated by its cognate ligand CD95L triggering programmed cell death. As a consequence, alterations in the CD95/CD95L pathway have been involved in several disease co...
Article
Endoplasmic Reticulum (ER) stress signaling is an adaptive mechanism triggered when protein folding demand overcomes the folding capacity of this compartment, thereby leading to the accumulation of improperly folded proteins. This stress signaling pathway is named the Unfolded Protein Response (UPR) and aims at restoring ER homeostasis. However, if...
Article
Despite its name, signalling induced by the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is versatile. Besides eliciting cell death by both apoptosis and necroptosis, TRAIL can also induce migration, proliferation, and cytokine production in cancerous and non-cancerous cells. Unravelling the mechanisms regulating the intri...
Article
Full-text available
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we sh...
Article
Full-text available
Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catal...
Article
Full-text available
Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1) ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-...
Chapter
The discovery of tumor necrosis factor (TNF) in 1975 paved the way to the description of a family of receptors, termed death receptors (DR), which are characterized by the presence of an intracellular death domain. During the twentieth century, several DR ligands were identified and, along with them, the diversity of cellular responses they could i...
Chapter
Resistance to death receptor ligands (such as FasL and TRAIL) and anticancer treatments is a hallmark of cancer cells. Alteration of sphingolipid (SL) metabolism is frequently observed in cancer cells and may contribute to resistance to stress-induced apoptosis. Ceramide, a biologically active sphingolipid, antagonizes cell growth and promotes apop...
Article
Ceramide, a biologically active sphingolipid in cell death signaling, accumulates upon CD95L treatment, concomitantly to apoptosis induction in Jurkat leukemia T cells. Herein, we show that ceramide did not increase in caspase-8 and -10-doubly deficient Jurkat cells in response to CD95L, indicating that apical caspases are essential for CD95L-trigg...
Article
Resistance to death receptor ligands (such as FasL and TRAIL) and anticancer treatments is a hallmark of cancer cells. Ceramide, a biologically active sphingolipid, antagonizes cell growth and promotes apoptosis and non-apoptotic forms of cell death. The intracellular levels of ceramide are highly regulated via complex metabolic pathways. Sphingomy...
Data
Toxicity of free MorG. Jurkat T cells (106/mL) were exposed to various concentrations of MorG (from 5 to 5000 nM) for 15 min at 37°C, then washed. Cells were irradiated (IR) or not (NI) as indicated in material and methods. Cell viability was evaluated using MTT assay after 24 h of culture. Results are means ± SD of 3 independent experiments. The r...
Data
Comparative binding of MorG on resting T lymphocytes and activated-T lymphocytes. T lymphocytes isolated from healthy donors were incubated for 48 h with anti-CD3 and anti-CD28 monoclonal antibodies and lymphocyte activation was controlled using staining with anti-CD25 monoclonal antibody. Activated T cells, resting T cells from the same donor and...
Data
The toxic effect of conjugate on fresh primary leukemia cells was confirmed using annexin V-FITC/PI staining and flow cytometry analysis. Fresh samples from patients with acute (ALL) or chronic (CLL) lymphoid leukemia were treated with TrMPyP-MorG and white light (1.7 J/cm2), as indicated in Figure 3. When the sample size permitted, the cell viabil...
Article
Full-text available
Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin...
Article
Full-text available
Upon CD95/Fas ligation, the initiator caspase-8 is known to activate effector caspases leading to apoptosis. In the presence of zVAD-fmk, a broad-spectrum caspase inhibitor, Fas engagement can also trigger an alternative, non-apoptotic caspase-independent form of cell death, which is initiated by RIP1. Controversy exists as to the ability of caspas...
Article
Full-text available
Ceramide can be converted into sphingomyelin by sphingomyelin synthases (SMS) 1 and 2. In this study, we show that in human leukemia Jurkat cells, which express mainly SMS1, Fas ligand (FasL) treatment inhibited SMS activity in a dose- and time-dependent manner before nuclear fragmentation. The SMS inhibition elicited by FasL (1) was abrogated by b...
Article
Marine environment has frequently afforded a variety of biologically active compounds with strong anticancer and cytotoxic properties. In the present study, the mechanism of action of Jaspine B, an anhydrophytosphingosine derivative isolated from the marine sponge Jaspis sp., was investigated. Jaspine B was able to dose- and time-dependently decrea...

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