The serine threonine kinase receptor-associated protein (STRAP) is a WD40 domain protein that regulates a wide array of biological processes. Previous reports suggest that STRAP possesses oncogenic characteristics and regulates signaling pathways associated with tumorigenesis. The aim of this dissertation was to investigate the functional role of STRAP in cellular proliferation and motility. I have shown that STRAP expression in fibroblasts promotes expression of the c-Jun proto-oncogene by inhibiting ubiquitin-mediated proteolysis. Stabilization of c-Jun was associated with increased expression of the AP-1 target gene, cyclin D1, and increased proliferation. These findings may suggest that STRAP-mediated AP-1 signaling can support tumor growth through cell autonomous and paracrine signaling. With respect to cellular motility, I have shown that STRAP appears to regulate persistent chemotaxis and tail formation during motility. Loss of STRAP expression was associated with increased cellular adhesion as well as alterations in the size and distribution of focal adhesion kinase (FAK) complexes. The results of this study suggest that STRAP promotes efficient chemotaxis through modulation of directionality and adhesion dynamics. Taken together, these studies provide insight into the potential mechanisms by which STRAP can promote tumor growth and metastasis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-06132011-093332 |
| Date | 30 June 2011 |
| Creators | Reiner, Jennifer |
| Contributors | Ann Richmond, Pran Datta, Pierre Massion, Brian Wadzinski |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-06132011-093332/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0025 seconds