Human β-catenin is a dual-functioned protein responsible for regulating cell-cell adhesion and gene transcription. To activate gene transcription, β-catenin must be shuttled into the nucleus where it interacts with various co-activators to activates gene transcription. Various studies have identified proteins that bind to specific amino acid sequences in β-catenin for proper gene transcription regulation. Compared to the single beta-catenin in most animals, C. elegans surprisingly contains four β-catenins. Though structurally similar, these beta-catenins became distinct during nematode evolution, resulting in four β-catenins that differ in functions. SYS-1 is one such β-catenin that loses its adhesion ability and is specialized in activating transcription of genes in the nucleus. Across different animals, β-catenin shares similar amino acid sequences and structure. SYS-1, while it shares the similar structure to other β-catenins, is the most divergent C. elegans beta-catenin when comparing amino acid sequences. In addition, while SYS-1 interacts with homologs of proteins that bind to and regulate human β-catenin, the binding sites of those proteins to SYS-1 is unknown. Here, we identify novel sites for beta-catenin’s gene transcription role within SYS-1 that greatly differed from human β-catenin. We also identify a novel mechanism for beta-catenin nuclear import, which is still largely unknown in any system, by identifying a candidate importer that associates with SYS-1 is required for SYS-1 dependent cell fate. In summary, though SYS-1 has a well-conserved function dictating cell fate in response to developmental signals, it has evolved novel regulatory, functional and localization mechanisms and therefore serves as a model for the plasticity nuclear importer that helps shuttle SYS-1 into the nucleus identified specific regions in SYS-1 that is involved in activating transcription which will result in cell fate changes.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-8422 |
| Date | 01 May 2019 |
| Creators | Wolf, Arielle Koonyee-Lam |
| Contributors | Phillips, Bryan T. |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | dissertation |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright © 2019 Arielle Koonyee-Lam Wolf |
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