xi, 93 p. ; ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / The atypical protein kinase C (aPKC) protein has been implicated in several human tumors yet very little is known about how aPKC is regulated. One mechanism that has been proposed as the possible source of several types of tumor is the defective asymmetric cell division of a small number of tumor stem cells. aPKC is required for cell polarization from nematodes to mammals, in tissues as diverse as epithelia, embryonic blastomeres, and neural progenitors. In Drosophila central nervous system, mitotic neural stem cells, termed neuroblasts, recruit the polarity proteins aPKC at the cell apical cortex. pack restricts the localization of the differentiation factors Miranda, Prospero, Brat, and Numb to the cell's basal cortex. Later during mitosis, the cytokinetic furrow sets unevenly about the neuroblast apical-basal axis to produce a large cell (neuroblast) which will continue to divide and self-renew, while the smaller ganglion mother cell inherits differentiation factors and terminally divides to give rise to a pair of neurons and/or glia.
Asymmetric cell division is not only critical for generating cellular diversity, it also ensures that a stable population of neural stem cell is constantly maintained while allowing neurogenesis to occur.
Despite its conserved role in cell polarity and tumorigenesis, relatively little is known about aPKC regulators and targets. In a co-authored work, I show that the small Rho GTPase, Cdc42, indirectly regulates aPKC. However, this stimulation is modest and the mutant phenotypes are not fully penetrant suggesting that other regulators exist.
To isolate other aPKC regulators and targets, I used a biochemical approach to identify aPKC-interacting proteins, and identified one positive regulator and one negative regulator of aPKC. I show that Dynamin-associated protein-160 (Dap160; related to mammalian Intersectin) is a positive regulator of aPKC. I also show that a regulatory subunit of protein phosphatase 2A (PP2A), negatively regulates aPKC. This dissertation includes both my previously published and my co-authored material. / Adviser: Chris Doe
| Identifer | oai:union.ndltd.org:uoregon.edu/oai:scholarsbank.uoregon.edu:1794/8330 |
| Date | 06 1900 |
| Creators | Chabu, Chiswili Yves, 1975- |
| Publisher | University of Oregon |
| Source Sets | University of Oregon |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | University of Oregon theses, Dept. of Biology, Ph. D., 2008; |
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