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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