Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 70-04, Section: B, page: 2016. Adviser: Dean Sheppard.

Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 70-04, Section: B, page: 2084. Adviser: David P. Toczyski.

<p> A complex molecular network is put into place at specific phases of the cell cycle to prevent unscheduled cell division that could result in malignant cell growth. Emerging evidence shows that still uncharacterized proteins play crucial functions at those cell cycle transition points. Nuclear protein Msp58 and EDD E3 ubiquitin ligase have been implicated in different aspects of cell proliferation and reported to be abnormally expressed in numerous types of cancers. The molecular mechanisms underlying Msp58 and EDD functions, however, are not well understood. The work presented here shows that Msp58 and EDD form a stable protein complex that regulates cell viability and proliferation. Interestingly, knockdown of EDD by RNA interference leads to a significant accumulation of Msp58 protein, which suggests that EDD serves as a negative regulator of Msp58. In addition, our in vivo ubiquitination assays and analyses of various cell lines treated with translational and proteasomal inhibitors demonstrate that Msp58 is regulated post-translationally by the ubiquitin-proteasome pathway. These results imply that EDD ligase activity is involved in this regulatory process. Using flow cytometry analyses and biochemical characterization of Msp58 and/or EDD depleted cells, we show that the Msp58-EDD complex plays important roles in cell cycle progression via the control of cyclin gene expression. In particular, silencing Msp58 and/or EDD alters the protein levels of cyclins B, D and E. Taken together, our data suggest that a set of the biological roles attributed to Msp58 and EDD may be executed in the context of the complex that they form, thereby revealing a novel molecular mechanism for these two proteins to accomplish their functions.</p>

<p> Through the use of a novel immunodetection assay, our lab identified a series of mutants that internally accumulate the precursor form of the vacuolar hydrolase carboxypeptidase Y (CPY), a phenotype that suggests a defect at the late e&barbelow;n&barbelow;dosome to v&barbelow;acuole (<i> ENV</i>) interface of the biosynthetic pathway. This study focuses on two of the novel genes identified: <i>ENV10</i> and <i>ENV11 </i> and is the first to establish the cellular localization of Env10p in the endoplasmic reticulum. Assays of vacuole and lipid droplet morphology, as well as growth characterization under various stressors demonstrate Env10p has a role in vacuolar protein trafficking and endomembrane system integrity and may operate in a parallel or compensatory manner to Env9p. This study also confirms that Env11p localizes to the nucleus in a saturable fashion where it may be involved in transcriptional regulation of genes involved in vacuole events in conjunction with Vid22p and Tbf1p.</p>

<p> Remodeling of the mouse mammary gland is a highly coordinated process that occurs after the removal of suckling pups from the mother. Involution, or shrinking of the mammary gland, after removal of the pups has been linked to apoptotic events within the mouse mammary tissue during forced weaning. Several transcription factors are hypothesized to be involved in this process. A transcription factor known as GATA-3, which was first identified in the thymus, is also important for maintenance of various tissue types within the mouse mammary gland; its loss leads to epithelial cell detachment and eventual death. Another transcription factor known as fetal zinc liver finger protein 1, or Fliz1, has been found to regulate GATA-3 in T-cells. This interaction had not been elucidated during involution in mouse mammary tissue. I hypothesized that Fliz1 is expressed at heightened levels during mouse mammary gland involution following forced weaning of pups, and that this expression correlates with a decrease in GATA-3 levels, with increased expression of the pro-apoptotic protein BAD. Using qRT-PCR, immunoblotting and immunohistochemistry I have shown that Fliz1 is indeed expressed in involuting mouse mammary gland tissue as well as several other tissue types. However, levels of Fliz1 remain fairly constant during involution. The findings also show that Cathepsin L, a known apoptotic marker for mammary gland involution, is substantially up-regulated during the process of mammary gland involution in the mouse. The study also revealed that GATA-3 levels as hypothesized decrease substantially during the process of mouse mammary gland involution, indicating that GATA-3 is required for maintenance of the mouse mammary gland.</p>

Thesis (Ph.D.)--Indiana University, Dept. of Biology, 2007. / Source: Dissertation Abstracts International, Volume: 68-05, Section: B, page: 2766. Adviser: Claire E. Walczak. "Title from dissertation home page (viewed Jan. 24, 2008)."

Thesis (Ph.D.)--University of California, San Francisco, 2005. / Source: Dissertation Abstracts International, Volume: 66-12, Section: B, page: 6424. Chairperson: Wendell A. Lim.

Thesis (Ph.D.)--University of California, San Francisco, 2006. / Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0040. Adviser: Christine Guthrie.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-05, Section: B, page: 2715. Adviser: Andrew Belmont. Includes bibliographical references (leaves 137-149) Available on microfilm from Pro Quest Information and Learning.

Thesis (Ph.D.)--University of California, San Francisco, 2007. / Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7132. Adviser: Barbara Panning.