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ROLE OF A NOVEL TRANSMEMBRANE PROTEIN, MTTS1 IN MITOCHONDRIAL REGULATION AND TUMOR SUPPRESSION
by
Poornima Murali
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
August 2012
Copyright 2012 Poornima Murali
Object Description
| Title | Role of a novel transmembrane protein, MTTS1 in mitochondrial regulation and tumor suppression |
| Author | Murali, Poornima |
| Author email | poornimm@usc.edu;muralipoornima@yahoo.in |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Molecular Microbiology and Immunology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-06-15 |
| Date submitted | 2012-08-03 |
| Date approved | 2012-08-03 |
| Restricted until | 2014-08-03 |
| Date published | 2014-08-03 |
| Advisor (committee chair) | Zandi, Ebrahim |
| Advisor (committee member) |
Schonthal, Axel H. Schönthal, Axel H. Landolph, Joseph R., Jr. |
| Abstract | A novel transmembrane protein was identified in Dr. Ebrahim Zandi’s lab as an IKK-β interacting protein by mass spectrometry. Mass spectrometry and IP (Immunoprecipitation) studies were performed to investigate functions of the newly identified protein. The study showed the interaction of this protein with two subunits of F1 components of mitochondrial ATP synthase. The F1 component of ATP synthase is the catalytic subunit that drives ATP synthesis. Further analysis showed that this protein localizes to mitochondria and has a probable role in regulating ATP synthesis by interacting with ATP synthase α and ATP synthase β. Research has shown that mitochondrial dysfunction has a predominant role in cancer progression. ❧ In this study, we characterized the role of this protein in regulating mitochondrial abundance and its subsequent role in tumor regulation. Based on the finding of this study regarding the function of the protein, we named it Mitochondrial Transmembrane Tumor Suppressor 1 (MTTS1). MTTS1 levels of 4 out of 7 lung cancer cell lines correlated with their respective mitochondrial abundance. A similar pattern was observed when 3 head and neck cancer cell lines were screened. Stable cell transfection to overexpress and knockdown MTTS1 was performed in HEK 293T cells (human embryonic kidney cells). Levels of many mitochondrial genes, responsible for cellular energy metabolism, were increased in HEK 293T cells overexpressing MTTS1. In-vivo studies in mice using HEK 293T cells showed that there was a significant delay in tumor growth in cells overexpressing MTTS1, suggesting that this protein can be a potential tumor suppressor. |
| Keyword | cancer; tumor supression; transmembrane protein; mitochondrial abundance |
| 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-m |
| Contributing entity | University of Southern California |
| Rights | Murali, Poornima |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-MuraliPoor-1139.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | ROLE OF A NOVEL TRANSMEMBRANE PROTEIN, MTTS1 IN MITOCHONDRIAL REGULATION AND TUMOR SUPPRESSION by Poornima Murali A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (MOLECULAR MICROBIOLOGY AND IMMUNOLOGY) August 2012 Copyright 2012 Poornima Murali |
