Cloning and functional characterisation of genes involved in cell death and cell survival

Abstract

During development and as a result of infection or injury, individual cells of multicellular organisms are required to mount appropriate survival or death responses. Two main signalling pathways are responsible for these outcomes. Apoptosis is a physiological cell death pathway responsible for a tightly controlled dismantling of cells and is regulated by a family of proteases called caspases. In opposition to this, the induction of the transcription factor NFkB results in the activation of a vast number of gene products which prevent cell death, promote immune responses and encourage cell growth and survival. The pathways of NFkB activation and caspase activation rely on interactions between effector proteins with distinctive domain structures. One such domain is the Caspase Recruitment Domain (CARD) domain, which facilitates protein-protein interactions between proteins in both caspase and NFkB induction pathways. As such, the CARD motif occupies a pivotal position in cell death and cell survival. This thesis explores the role of two CARD proteins, NAC and ASC, in these pathways.