Date of Degree
Access restricted until 07/29/2021
PhD (Doctor of Philosophy)
Molecular and Cell Biology
Phillips, Bryan T
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
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.
asymmetric cell division, b-catenin, nuclear export, nuclear import, SYS-1, transactivation
xi, 101 pages
Includes bibliographical references (pages 92-101).
Copyright © 2019 Arielle Koonyee-Lam Wolf
Wolf, Arielle Koonyee-Lam. "Nuclear localization and transactivation of sys-1/β-catenin, a regulator of Wnt target gene expression and asymmetric cell division." PhD (Doctor of Philosophy) thesis, University of Iowa, 2019.
Available for download on Thursday, July 29, 2021