How Toxoplasma gondii induces c-Myc, a pivotal host oncogene
Abstract/Contents
- Abstract
- Regulation of host transcription is a common strategy of intracellular microorganisms to control their host cell. The obligate intracellular parasite, Toxoplasma gondii, secretes specific effectors that alter host transcription and regulate various cellular processes. This thesis explores a novel interaction of this apicomplexan with its host that involves the induction of one of the most pivotal host transcription factors, c-Myc. Given the far-reaching role of c-Myc in essential host processes, e.g. cell cycle, apoptosis, metabolism, and immune function, it is likely that the regulation of this protein has profound consequences on the cell and is therefore one of the factors determining the outcome of Toxoplasma infection. This thesis presents evidence that Toxoplasma dramatically increases the expression of host c-Myc in infected cells and that this induction likely alters the host transcription program as numerous c-Myc targets are regulated during Toxoplasma infection. Moreover, a genetic screen that led to the isolation of Toxoplasma mutants defective in c-Myc induction and subsequent identification of a novel Toxoplasma effector, MYR1 (MYc Regulator 1), is described here. The data strongly suggest that MYR1 controls not only the expression of c-Myc, but also carries an additional function in regulating the expression of Major histocompatibility complex (MHC) class II in infected cells. Remarkably, MYR1 mutants (although derived from a highly virulent strain of Toxoplasma) exhibit decreased virulence in mice showing that this parasite factor has an evident effect on the outcome of the infection. Finally, an intriguing observation that the infection by a closely related parasite Neospora caninum leads to a completely opposite effect on c-Myc levels is presented, offering an insight into how these two parasites have evolved to control their cell and revealing a potential explanation for their distinct host range and immunopathology.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Franco, Magdalena |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Boothroyd, John C |
| Thesis advisor | Boothroyd, John C |
| Thesis advisor | Felsher, Dean (Dean Walton) |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Sarnow, P. (Peter) |
| Advisor | Felsher, Dean (Dean Walton) |
| Advisor | Monack, Denise M |
| Advisor | Sarnow, P. (Peter) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Magdalena Franco. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Magdalena Franco
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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