"March 2003" Bibliography: leaves 206-233. The experimental data presented in this thesis provide evidence that PTP-Pez is an active phosphatase that interacts with and dephosphorylates the adherens junction protein ℓ-catenin. PTP-Pez also associates with proteins that form part of the tight junction complex, the scaffolding protein ZO-1 and the transmembrane protein occludin.

The mitotic spindle checkpoint plays a critical role during the cell cycle by protecting the faithful transmission of chromosomes during mitosis. If chromosomes are improperly bound to the spindle microtubules the checkpoint will prevent progress to anaphase by temporarily arresting cells in metaphase until all the chromosomes are correctly aligned. Bub1b is an essential component of the mitotic spindle checkpoint that transiently localises to kinetochores during mitosis and becomes phosphorylated, a response that is sustained during mitotic arrest. Bub1b has been implicated in other processes related to mitotic progression and is thought to regulate mitotic timing and have a role in caspase mediated cell death after prolonged mitotic arrest. The development of aneuploidy and cancer has been associated with mutations in the BUB1B gene and reduction in the level of Bub1b protein. To further our understanding of Bub1b function in the spindle checkpoint and mitosis, new protein interactions involving Bub1b were identified. This thesis describes the search for alternative proteins that interact with Bub1b, and their function in the mitotic spindle checkpoint and regulation of Bub1b activity. Using a yeast two-hybrid approach, members of the B56 family of regulatory subunits of serine-threonine protein phosphatase (PP2A) were identified as novel interacting partners of Bub1b. Substrate specificity of PP2A is determined by the regulatory subunits. There are five characterised isoforms of the B56 family, each encoded by separate genes. In addition, some isoforms have several recognised splice variants. Confirmation of interactions by alternative methods demonstrated that the isoforms B56γ and B56[epsilon] preferentially interact with phosphorylated Bub1b, whereas the interaction of the remaining B56 isoforms (α, β and [delta]) occurs at a lower affinity with no specificity for the phosphorylated form. It was further demonstrated that B56γ1 associated with phosphorylated Bub1b in vivo. Induced overexpression of splice variants of B56γ1 and B56γ2 demonstrated a significant reduction in levels of phosphorylated Bub1b during mitotic spindle checkpoint activation. In addition, an associated lower mitotic index was evident in cells with B56γ1 overexpression. Specific inhibition of PP2A activity with okadaic acid was shown to prolong Bub1b phosphorylation during normal mitosis and to restore the levels of phosphorylated Bub1b in arrested cells over expressing B56γ. These findings suggest a role for PP2A activity in regulation of Bub1b function that is mediated through substrate recognition by B56 regulatory subunits.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "May 2001." Typescript. Vita. Includes bibliographical references (leaves 143-156). Also available on the Internet.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2003. / "March 2003" Bibliography: leaves 206-233.

Thesis (Ph.D.)--Kent State University, 2007. / Title from PDF t.p. (viewed Mar. 12, 2009). Advisor: Srinivasan Vijayaraghavan. Keywords: sperm, testes, spermatogenesis, protein phosphatase, knock out, spermatid. Includes bibliographical references (p. 115-129).

Thesis (Ph.D.)--Kent State University, 2008. / Title from PDF t.p. (viewed May 26, 2009). Advisor: Srinivasan Vijayaraghavan. Includes bibliographical references (p. 127-136).

Thesis (Ph. D.)--University of Virginia, 2000. / Spine title: Role of REGL in glucose repression. Includes bibliographical references (p. 194-220). Also available online through Digital Dissertations.

Thesis supervisor: Stefan Strack. Includes bibliographic references (p. 77-88).

Berlin, Freie University, Diss., 2004. / Text in engl. Sprache. - Dateiformat: zip, Dateien im PDF-Format.

Respiratory syncytial virus (RSV) is a pathogen associated with lower respiratory tract infection, and is a common cause of infant hospitalization worldwide. Despite efforts to create safe and cost-effective RSV therapeutics, there remains no vaccine, and antiviral drugs have been developed with limited success. Among the 11 proteins coded by the negative-sense single-stranded RNA genome of RSV, the phosphoprotein (P) and nucleoprotein (N) aid in the formation of an RNA-dependent RNA polymerase (RdRp) complex, which is essential for RSV virulence. The specificities of the N-P binding interaction have been researched extensively, which has provided researchers with a novel target for an RSV therapeutic. In this study, a recombinant peptide mimetic (P220-241) containing the final 21 C-terminal amino acids of RSV P fused to Maltose-Binding Protein (MBP), and a cell-penetrating peptide (CPP), was purified for the purpose of targeting this interaction. In addition to successfully entering cells, the peptide was shown to inhibit both RSV subtype A and subtype B infection in vitro, with a percent inhibition (PI) of infection as high as 95% at 20 μM. Additionally, P220-241 did not inhibit infection of parainfluenza virus type 2 (PIV-2), indicating this inhibition was not an artifact of the peptide acting as a pathogen-associated molecular pattern (PAMP). A series of three different assays demonstrated that P220-241 does not appear to have any cytotoxic effects in vitro. Finally, using both glutathione S-transferase (GST) pull-downs and in vitro immunoprecipitations, we demonstrated that P220-241 is able to bind the N protein, while also preventing binding of full-length P protein. Taken together, this study provides the framework for a novel method of targeting RSV protein-protein interactions using chimeric cell-penetrating peptide mimetics. / Thesis / Master of Science (MSc)