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Dissertation
Proteomic Profiling of the Oncogenic Septin 9 Reveals Isoform-Specific Interactions and Functions in Breast Cancer Cells
Doctor of Philosophy (Ph.D.), Drexel University
Oct 2021
DOI:
https://doi.org/10.17918/00000899
Abstract
Proteins in cells do not act in isolation and septins are no exception. Septins associate with other septins and non-septin biomolecular partners to impart their influence on myriad of dynamic cellular processes such as the cell cycle and structures such as the cytoskeleton. Though several studies probing the interactome of septin 9 (SEPT9) have been performed, little is known about the molecular interactions and pathways of SEPT9 isoforms, and how they contribute to the development and metastasis of breast cancer. In Chapter 1, I provided a comprehensive review of SEPT9, an essential and ubiquitously expressed septin with multiple isoforms and altered expression in breast cancer and other diseases including neurological disorders. In Chapter 2, we investigated isoform-specific molecular interactions of SEPT9. Using comparative shotgun proteomics, we identified and mapped the interactomes of SEPT9 isoforms 1, 4 and 5 into spatial and functional networks and subnetworks. We revealed isoform-specific interactions with proteins of distinct subcellular localizations and functions, implicating SEPT9 isoforms in hitherto unknown mechanisms of tumorigenesis. We hypothesized that truncations in the N-terminal sequences of SEPT9 isoforms bestow a functional specialization by biasing toward specific septin and non- septin binding partners. Our results provide rare evidence for septin isoform-specific interactions, which can benefit future work on the oncogenic functions and therapeutic targeting of SEPT9. Finally, in Chapter 3, I explored the challenges, considerations and lessons learned when embarking on a proteomics project to identify protein interaction partners. This chapter includes a critical appraisal of the methodologies.
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Details
- Title
- Proteomic Profiling of the Oncogenic Septin 9 Reveals Isoform-Specific Interactions and Functions in Breast Cancer Cells
- Creators
- Louis Joseph Devlin
- Contributors
- Elias Spiliotis (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 237 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991016457359104721