Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program
Microtubules; Cytoskeleton; Microtubule-Associated Proteins; Cell Cycle Proteins; Neoplasm Proteins; Tumor Suppressor Protein p53; Protein-Serine-Threonine Kinases; Cytokinesisl; Centrosome; Academic Dissertations; Dissertations, UMMS
Life Sciences | Medicine and Health Sciences
A complex network of protein filaments collectively known as the cytoskeleton carries out several crucial cellular processes. These functions include, but are not limited to, motility, cell shape, mitosis and organelle trafficking. The cytoskeleton is also highly responsive, allowing the cell to alter its shape in response to its immediate needs and environment. One of the major components of the cytoskeleton is the microtubule network. To refer to the array of micro tubules in the cell as a skeleton is a misnomer. Microtubules, by virtue of their structure and nature, are highly dynamic, continuously growing and shrinking. They also bind a variety of accessory molecules that aid in regulating and directing their dynamic activity. In this way they provide a structural basis for integral cell functions that require rapid assembly and disassembly. In some cases, perturbations of the microtubule network results in structural anomalies that lead to undesirable outcomes for the cell, namely chromosomal missegregation events and instability. The accumulation of these events may induce aneuploidy, which has been a fundamental component of tumorigenesis. This dissertation examines the role of the microtubule cytoskeleton within three distinct contexts. The first chapter investigates the association of the anti-apoptotic protein survivin with the microtubule network and its potential impact upon the cell from interphase to cytokinesis. The second chapter of this dissertation explores a little-studied, microtubule-dense organelle, referred to as the midbody, and the highly orchestrated events that take place within it during cytokinesis. The third and final chapter describes a unique experimental condition that may further our understanding of the interaction between the tumor suppressor p53 and the centrosome in cell cycle regulation and tumorigenesis.
Rosa, Jack, "Perturbation and Modulation of Microtubule Cytoskeletal Elements in Response to the Potentially Oncogenic Molecules, Survivin and P53, and Cytokinesis: A Dissertation" (2006). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 280.