Lipides, Nutrition, Cancer
SÉminaires LNC
AnnÉe 2017

Intervenant : Dr Elodie Lafont


Date :12 Juin 2017 14h00
Lieu : Faculté de Médecine - Salle 224
Sujet :

LUBAC and linear ubiquitin regulate TRAIL-induced apoptosis, necroptosis and gene activation

Background:Ubiquitination is a post-translational modification which influences multiple signalling pathways. Ubiquitin itself can be the target of ubiquitination, leading to the formation of different di-ubiquitin linkages, depending on which amino acid on the target-attached ubiquitin is used for the linkage to the C-terminus of the incoming ubiquitin. Apart from the seven lysines present in ubiquitin, also the amino group on the N-terminal methionine (M1) of ubiquitin can be used to link two ubiquitins, forming linear or M1-linked chains. The linear ubiquitin chain assembly complex (LUBAC) is the only E3-ligase known to date to form M1-linked ubiquitin chains de novo. LUBAC is composed of HOIL-1, SHARPIN and the catalytically active component HOIP. It has been shown to be crucial for regulating gene activation and cell death downstream of TNFR1 as well as several other innate and adaptive immune signalling pathways. We found that LUBAC forms part of the TRAIL-R-associated complex I as well as of the cytoplasmic TRAIL-induced complex II, two platforms which both trigger cell death and gene activation (1). Our latest results on the molecular mechanisms underlying the roles of LUBAC and M1-ubiquitination in the context of TRAIL signalling will be presented.


Selected publications:

1 Lafont, E., Kantari-Mimoun, C., Draber, P., De Miguel, D., Hartwig, T., Reichert, M., Kupka, S., Shimizu, Y., Taraborelli, L., Spit, M., Sprick, MR., Walczak, H. The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death, EMBO J (2017)
2 Hartwig T, Montinaro A, von Karstedt S, Sevko A, Surinova S, Chakravarthy A, Taraborrelli L, Draber P, Lafont E, Arce Vargas F, El-Bahrawy MA, Quezada SA, Walczak H. The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2. Mol Cell. (2017)

3 Draber P, Kupka S, Reichert M, Draberova H, Lafont E, de Miguel D, Spilgies L, Surinova S, Taraborrelli L, Hartwig T, Rieser E, Martino L, Rittinger K, Walczak H. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes. Cell Rep. (2015)

Invitation: Olivier Micheau - UMR1231

Le séminaire aura lieu à la faculté de médecine -Salle 224 - à 14h00

Renseignements - omicheau@u-bourgogne.fr Tel: 03 80 39 34 68