Study of the role of the DUBA/UBR5 complex in TNF-induced cell death and survival signaling

TNF (tumor necrosis factor) is a pleiotropic cytokine acting via two receptors on the cell membrane, TNFR1 and TNFR2. Cytokines are proteins that have a communication function between cells and play, amongst others, an important role in inflammatory and immunological reactions. TNF receptors transmit signals leading to inflammatory gene activation and cell death, and consequently are involved in different inflammatory pathologies such as arthritis, psoriasis and inflammatory bowel disease. Therefore, inhibition of TNF signaling is an important therapeutic target in the management of these diseases. Most of the detrimental effects of TNF are caused by TNFR1 signaling. Because general inhibition of TNF signaling during therapy evokes detrimental side effects it is important to thoroughly understand how specific TNFR1-dependent signaling pathways are controlled in order to allow better, more precise, targeting of this pathway. We identified novel molecules controlling TNFR1-induced cell death, which we will further study during this project.