A Model for Simian Virus 40 Small Tumor Antigen Expression in Drosophila Melanogaster
| dc.contributor.advisor | Megraw, Timothy | en |
| dc.creator | Kotadia, Shaila Rajni | en |
| dc.date.accessioned | 2010-07-12T17:37:16Z | |
| dc.date.available | 2010-07-12T17:37:16Z | |
| dc.date.issued | 2009-01-14 | |
| dc.description.abstract | Viruses of the DNA tumor virus family share the ability to transform vertebrate cells through the action of virus-encoded tumor antigens that interfere with normal cell physiology. They accomplish this very efficiently by inhibiting endogenous tumor suppressor proteins that control cell proliferation and apoptosis. Simian Virus 40 (SV40) encodes two oncoproteins, large tumor antigen (LT), which directly inhibits the tumor suppressors p53 and Rb, and small tumor antigen (ST), which interferes with serine/threonine protein phosphatase 2A (PP2A). We have constructed a Drosophila model for SV40 ST expression and show that ST induces supernumerary centrosomes, an activity we also demonstrate in human cells. In early Drosophila embryos, ST also induced increased microtubule stability, chromosome segregation errors, defective assembly of actin into cleavage furrows, cleavage failure, a rise in cyclin E levels, and embryonic lethality. Using ST mutants and genetic interaction experiments between ST and PP2A subunit mutations, we show that all of these phenotypes are dependent on ST's interaction with PP2A. After characterizing the effects of ST on the cell cycle, we utilized the Drosophila model to further study ST. Through proteomics, we discovered ST binds the kinesin-1 motor, leading to inactivation of motor activity. Using genetic interactions, we showed that ST genetically interacts with a cyclin E mutant and overexpressed cyclin E. Together, these analyses demonstrate novel properties for ST and the validity and utility of Drosophila as a model for viral oncoprotein function in vivo. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 759862864 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/333 | |
| dc.language.iso | en | en |
| dc.subject | Simian virus 40 | en |
| dc.subject | Protein Phosphatase 2 | en |
| dc.subject | Antigens, Neoplasm | en |
| dc.title | A Model for Simian Virus 40 Small Tumor Antigen Expression in Drosophila Melanogaster | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2010-01-14 | |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Genetics and Development | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |