Genetic susceptibility in complex diseases: genes involved in T-cell lymphoblastic lymphoma development.
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)
DESCRIPTION OF THE OFFER
INFLUENCE OF FADD PHOSPHORYLATION IN PROTEIN STABILITY.
Our group is interested in the study of genetic and epigenetic alterations involved in T-cell lymphoblastic lymphoma (T-LBL). This is an aggressive tumour type derived from immature thymocytes in diverse stages of differentiation (Cortelazzo et al. 2011). Although FADD canonical function is as a principal adaptor in apoptotic signalling, it has become evident that FADD has a non-apoptotic role related to proliferation and cell cycle control which seems to depend on its phosphorylation status (Hua et al. 2003). Total FADD and phosphorylated FADD are reduced in mouse T-LBL (Marin-Rubio et al. 2016), which may serve, if confirmed in human T-LBL, as a prognostic marker. However, the exact mechanisms whereby FADD phosphorylation regulates its non-apoptotic function have not been elucidated. It has been reported that serine-phosphorylation may affect protein stability and, in turn, protein function (Chen et al. 2012). We want to determine if such is the case for FADD. Our hypothesis is that FADD phosphorylation status may influence its stability. To test this hypothesis, we propose the present offer for TFM, whereby the student will challenge the stabilization and degradation of FADD protein in stable cell lines expressing wild-type, phosphomimetic or non-phosphorylatable FADD.