DOI

10.17077/etd.3tly-c0lv

Document Type

Dissertation

Date of Degree

Spring 2019

Access Restrictions

Access restricted until 07/29/2021

Degree Name

PhD (Doctor of Philosophy)

Degree In

Molecular and Cell Biology

First Advisor

Phillips, Bryan T

First Committee Member

Slusarski, Diane

Second Committee Member

Houston, Douglas

Third Committee Member

Cornell, Robert

Fourth Committee Member

Smolikove, Sarit

Abstract

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.

Keywords

asymmetric cell division, b-catenin, nuclear export, nuclear import, SYS-1, transactivation

Pages

xi, 101 pages

Bibliography

Includes bibliographical references (pages 92-101).

Copyright

Copyright © 2019 Arielle Koonyee-Lam Wolf

Available for download on Thursday, July 29, 2021

Included in

Cell Biology Commons

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