This application addresses the interactions between Fas signalling and the cell cycle control machinery and is driven by our preliminary observations that normal thymocytes and cycling T-cell blasts are differentially susceptible to Fas-induced apoptosis in the G1 phase. In the present application, the investigator wants to address the following questions. Through what signalling pathway does Fas signalling act on cell cycle control? Does this pathway transmit effects distinct from the apoptotic signal transmitted through the cysteine protease cascade? Does the signalling pathway that converges on the G1/S cell cycle checkpoint actually modulate the susceptibility of cells to death? The outcome of this research program will be a detailed molecular understanding of the interactions between Fas and cell cycle control.
