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dc.contributor.authorVandenberg, Laura Joanna
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2011-06-10 13:15:37.081en
dc.date.accessioned2011-06-14T14:53:59Z
dc.date.available2011-06-14T14:53:59Z
dc.date.issued2011-06-14T14:53:59Z
dc.identifier.urihttp://hdl.handle.net/1974/6552
dc.descriptionThesis (Master, Biochemistry) -- Queen's University, 2011-06-10 13:15:37.081en
dc.description.abstractVascular smooth muscle cell migration is a significant contributor to many aspects of heart disease, and specifically atherosclerosis. Tissue damage in the arteries can result in the formation of a fatty streak. Smooth muscle cells (SMC) can then migrate to this site to form a fibrous cap, stabilizing the fatty plaque. Since cardiovascular disease is the leading cause of death in developed countries, this function of SMC is an essential area of study. The formation of lamellipodia and circular dorsal ruffles were studied in this project as indicators that cell migration is occurring. The roles of the proteins p53, Rac, caldesmon and PTEN were investigated with regards to these actin-based structures. The tumour suppressor p53 is often reported to cause apoptosis, senescence or cell cycle arrest when stress is placed on a cell, but has recently been shown to regulate cell migration as well. It was determined in this project that p53 could inhibit the formation of both lamellipodia and circular dorsal ruffles. It was also shown that this could occur directly through an inhibition of the GTPase Rac. Previous studies have shown that p53 can upregulate caldesmon, a protein which is known to bind to and stabilize actin filaments while inhibiting Arp2/3-mediated branching. It was confirmed that p53 could upregulate caldesmon, and that caldesmon could inhibit the formation of lamellipodia and circular dorsal ruffles. The phosphorylation of caldesmon by p21-associated kinase (PAK) or extracellular signal-related kinase (Erk) was shown to effectively reverse the ability of caldesmon to inhibit these structures. The role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was also studied with regards to this signalling pathway. PTEN was shown to inhibit lamellipodia and circular dorsal ruffles through its lipid phosphatase activity. It was concluded that p53 can inhibit the formation of lamellipodia and circular dorsal ruffles in vascular SMC, and that this occurs through Rac, caldesmon and PTEN.en
dc.languageenen
dc.language.isoenen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectp53en
dc.subjectCaldesmonen
dc.subjectPTENen
dc.subjectLamellipodiaen
dc.subjectCircular Dorsal Rufflesen
dc.subjectCell Migrationen
dc.subjectRacen
dc.subjectErken
dc.subjectPAKen
dc.titlep53 Regulates the Formation of Lamellipodia and Circular Dorsal Ruffles Through Caldesmon and PTENen
dc.typeThesisen
dc.description.degreeMasteren
dc.contributor.supervisorMak, Alanen
dc.contributor.departmentBiochemistryen


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