p53 Regulates the Formation of Lamellipodia and Circular Dorsal Ruffles Through Caldesmon and PTEN

Vascular 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.

Dispossessing bare life: Towards a theoretical framework for examining power relations through economic development at the 2010 FIFA World Cup in South Africa

In the past twenty years an increasing number of Global South nations have vied for the rights to host prestigious and expensive sport mega events. This trend requires significant reflection given the enormous economic costs of these events, which often produce little capital gain for the host nation (Whitson & Horne, 2006). Furthermore, sport mega events are often utilized for their symbolic capital (Belanger, 2009), which sometimes manifests through forcing people from their land for the sake of “beautification” (Davis, 2006). In this project, then, I asked how technologies of power were utilized by FIFA, corporate stakeholders, and the South African government to control people who were marginal to, or impeded the success of, the World Cup in Nelspruit, South Africa. This project consisted of two parts: the first involved constructing a theoretical framework for better understanding power as it operates through sport mega events in general. To this end I employed Marxian notions of the ordering of physical space, Foucauldian conceptions of sovereignty and governmentality, and Agamben’s (1998) state of exception to determine how particular bodies are constituted and controlled through sport mega events. In the second part, I applied this theoretical framework to the events in South Africa to better elucidate how people became displaced and killed because of the 2010 FIFA World Cup. I used South African popular news and documentaries as empirical evidence and conducted a discursive analysis of said news media. Through this coverage it became apparent that the mega event created the conditions in which new forms of rogue sovereign partnerships could arise through a historically and spatially contingent process of capitalism. The rogue sovereigns’ para-juridico-political orders, the discourses and practices of accumulation by dispossession as a tactic and effect of govermentality, and other historical non-capital subjectivities such as racial identity, all contributed to constituting Agamben’s state of exception in which people could be displaced, killed or left to die in the events surrounding the World Cup.