Year: 2001
Type: dissertation
Abstract: Apoptosis or programmed cell death (PCD) is an evolutionarily conserved cellular process that is essential for normal development and homeostasis of multicellular organisms. Defects in the apoptosis signaling result in many diseases including autoimmune diseases and cancer. 'Caspases' (c_ysteinyl aspartate proteases ) are mammalian homologues of 'ced-3', a first pro-apoptotic gene found in the nematode 'Caenorhabditis elegans'. They are the executioners of apoptosis and 'Casapse-3' has the closest sequence homology to 'ced-3'. To better understand the role of 'caspase-3 in vivo', a genetic approach was taken to generate 'caspase-3' knockout (KO) mice. The findings presented in chapter two demonstrate that ' caspase-3' is required for activation induced cell death of peripheral T cells. In addition, experiments using different cell types with different death stimuli demonstrate that requirement for 'caspase-3' in apoptosis is context and cell type specific. Chapter 3 presents evidence that 'caspase-3' is required for Fas-mediated cell death of hepatocytes 'in vivo'. Furthermore, we demonstrate that ' caspase-3' plays a regulatory role in addition to the conventional executionary role in the apoptotic pathway. Data presented in chapter 4 illustrates a novel role of 'caspase-3' in cell cycle regulation. In peripheral B cells of 'caspase-3' KO mice, hyperproliferation without a primary defect in cell death is observed. Further examination showed that these activated 'caspase-3' null B cells have abnormal parameters of proteins involved in cell cycle regulation. These findings illustrate the complex role of 'caspase-3 in vivo' that need to be elucidated for ideal therapeutic designs for many diseases that result from defective apoptosis.
Author: Minna Woo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2789760777