Regulation of the pro-inflammatory cytokine IL-1β by ubiquitination and its role in modulating IL-1β activity

Abstract

Interleukin-1 beta is a potent proinflammatory cytokine that requires inflammasome-associated caspase-1, a cysteine protease, to cleave inactive precursor IL-1beta, to its active secreted p17 fragment. Excessive IL-1beta activation and release promotes autoinflammatory diseases, such as Cryopyrin associated periodic syndromes (CAPS), gout and cancers. Despite this role in inflammatory disease, the post-translational regulation of IL-1beta is poorly understood. This thesis studies the post-translational modifications (PTMs) of IL-1beta, with a particular focus on the ubiquitination of precursor IL-1beta and its role in modulating IL-1beta activity.