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SEX-SPECIFIC EFFECTS OF DROSOPHILA p53 ON ADULT LIFE SPAN
by
Jie Shen
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR BIOLOGY)
August 2009
Copyright 2009 Jie Shen
Object Description
| Title | Sex-specific effects of drosophila p53 on adult life span |
| Author | Shen, Jie |
| Author email | jieshen007@gmail.com; jies@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Biology |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2009-04-29 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-07-07 |
| Advisor (committee chair) | Tower, John |
| Advisor (committee member) |
Forsburg, Susan Longo, Valter Mak, Chi |
| Abstract | Aging is a process of gradual decline of normal function and increase of chance of mortality in an organism over time. Recent aging research has shown that conserved pathways are shared between Drosophila and other model organisms. One of the main evolutionary theories of aging is the antagonistic pleiotropy theory, that predicts that there are antagonistically pleiotropic genes (AP genes) that can be both beneficial and harmful at different stages of the life cycle. To test this, the effects of p53 on Drosophila life span were examined, using a system for experimentally controlling gene expression called “GeneSwitch”. p53 was found to be an AP gene, with sex-specific and tissue-specific effects on fly life span. Nervous-system-specific over-expression of p53 in adult flies gave a life span extension to females, but a decrease of life span in males. Tissue-general over-expression of p53 in adult flies gave the opposite pattern: a life span extension to males, but a decrease of life span in females. These results suggest that p53 has both tissue-specific and sexually antagonistic effects on fly life span. Over-expression of other apoptosis-regulatory genes did not increase life span, suggesting that p53 regulation of apoptosis may not be the mechanism by which p53 affects fly life span. The IIS pathway was found to be involved in determining the sex-specific effects of p53. In a foxo null background, the effect of p53 in males was converted to the female-like pattern. In addition, over-expression of p53 was found to alter signaling through the IIS pathway in a sex-specific way, as indicated by AKT phosphorylation levels. The effects of p53 over-expression on life span were reduced in a Sir2 null mutant background, indicating that the Sir2 pathway regulates the magnitude of p53 effects. Finally, the effects of sex-differentiation genes on life span were explored.; The data suggest that genes in the sex-determination and differentiation pathway interact with IIS and Sir2 to produce the sex-specific effects of p53. |
| Keyword | drosophila; aging; p53; apoptosis; sex-differentiation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2329 |
| Rights | Shen, Jie |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-shen-2907 |
| Archival file | uscthesesreloadpub_Volume14/etd-shen-2907.pdf |
Description
| Title | Page 1 |
| Full text | SEX-SPECIFIC EFFECTS OF DROSOPHILA p53 ON ADULT LIFE SPAN by Jie Shen A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR BIOLOGY) August 2009 Copyright 2009 Jie Shen |
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