CYCLIN DEPENDENT KINASES IN LIVER REGENERATION AND PHYSIOLOGY

Abstract

Cyclin-dependent kinase 1 (CDK1) and cyclin A2 are two important regulators of the cell cycle. In this thesis, I investigate the cell cycle-dependent and -independent functions of CDK1 and cyclin A2 in the context of the liver using liver-specific CDK1 and cyclin A2 knockout mouse models. My findings suggest biliary epithelial cell (BEC) or hepatic progenitor cell (HPC) originated hepatocyte contribution to liver regeneration in CDK1 knockout mice. I propose that Tspan8, a novel marker I identify for differentiating bi-phenotypic hepatocytes, can contribute to further studies on alternative therapeutic options for severe liver disease patients. My findings also suggest that in cyclin A2 knockout mice, where some kinase functions of CDK1 and CDK2 are abolished simultaneously, even though AKT is functional there are abnormalities in its rhythmic activation. I propose that cyclin A2 deletion may lead to problems in the intrinsic regulation of daily AKT activity which needs further investigation.