Apoptosis is a programmed cell death process essential for development and homeostasis and its deregulation is involved in many diseases. The caspases are a family of cysteine proteases present as inactive pro-enzymes in all cell types and activated following apoptotic stimulation. These proteases cleave a particular subset of protein substrates which results in the organized break down of the cells which shrink and are cleared through phagocytosis. In this thesis, many apoptotic processes are discussed. First, the CEACAM1-L cell-cell adhesion molecule is identified as a caspase-3 substrate during apoptosis. This cleavage event alters CEACAM1-L adhesion properties which might affect apoptotic cell clearance. Second, the brain development defect phenotype of Caspase-3-null mice is investigated. The mouse strain specificity of that mutation allowed the identification of caspase-7 as a compensating enzyme for the loss of caspase3 in precursor neurons. Finally, new functions are elucidated for Hippi, a pro-apoptotic molecule involved in the neurodegenerative Huntington's disease. Hippi-targeted deletion revealed its role in node cilia assembly and in Sonic hedgehog signaling during early mouse embryo development. Altogether, these findings provide new insights into several aspects of the apoptosis program.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85558 |
| Date | January 2005 |
| Creators | Houde, Caroline |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198780, proquestno: AAINR12859, Theses scanned by UMI/ProQuest. |
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