Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 236-251). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2004. / Vita. Bibliography: 82-95.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 155-195.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 90-110).

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 121-135).

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Membrane adaptor proteins are characterized by the lack of enzymatic activity and the presence of various interaction sites for other proteins and cellular membranes. They typically function as scaffolds connecting receptors or other adaptors with proximal signaling molecules at cellular membranes. Their overall effects on signaling can be activating or inhibiting depending on the nature of the effector molecules they recruit. SCIMP is one of the membrane adaptors discussed in this thesis. It is expressed in antigen- presenting cells and it has been previously shown to enhance MHCII signaling in B cells. This thesis covers the analysis of SCIMP functions beyond B cells and describes the first analysis of SCIMP deficient mice. Although the results of this analysis did not show any alterations in immune cell populations, the novel function of SCIMP in dendritic cell signaling downstream of DECTIN- 1 was uncovered. DECTIN-1 is a pattern recognition receptor involved in antifungal immunity. The data presented in this thesis describe the role of SCIMP in sustaining DECTIN-1 signaling over relatively long periods of time and the contribution of SCIMP signaling to maintaining prolonged production of pro-inflammatory cytokines. PSTPIP2 is another interesting adaptor discussed in this thesis. It is...

<p>  </p> <p>Ubiquitination is a post-translational modification that activates a variety of signaling pathways. The process of tagging ubiquitin (Ub) onto a substrate protein requires three proteins. First, the E1-activating protein primes Ub for attachment to the E2-conjugating enzymes. The E2-conjugating enzyme then brings Ub to E3 ligases, which also recruit the substrate proteins. The final step of this cascade is the transfer of Ub onto the substrate protein. More commonly, ubiquitinated proteins are then degraded via the proteasome. This cascade to downregulate proteins is employed as a cellular adaptation mechanism in response to various threats, including bacterial and viral pathogens. Although the Ub system exists exclusively in eukaryotes, in recent years many bacterial effector proteins and viral factors have been shown to hijack the system through highly regulated mechanisms. In my Ph.D. work, I characterized the hijacking mechanism of a protein produced by human papillomavirus (HPV) that causes downregulation of p53. Downregulation of p53 leads to the oncogenic effects of HPV infection. A strain of oncogenic HPV, HPV-16, produces the E6 protein, which forms a complex with the human ubiquitin E3 ligase, E6AP. This allows E6AP to recognize p53 for ubiquitination. Furthermore, the ability of E6 to act as an adaptor protein to target unnatural substrate proteins has been employed by medicinal chemists as the basis of <u>pro</u>teolysis <u>ta</u>rgeting <u>c</u>himeras (PROTACs). To this extent, my thesis covers three broad ideas that will add to our understanding of <strong>1) Cellular adaptor protein regulation, 2) viral adaptor protein hijacking, and 3) PROTAC ligand development.</strong></p>

Thesis (Ph. D.)--University of Virginia, 2008. / Title from title page. Includes bibliographical references. Also available online through Digital Dissertations.