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A Novel Role of the Ankyrin-Binding Motif of L1-Type CAM Neuroglian in Nuclear Import and Transcriptional Regulation of Myc
| Title: | A Novel Role of the Ankyrin-Binding Motif of L1-Type CAM Neuroglian in Nuclear Import and Transcriptional Regulation of Myc. |
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| Name(s): |
Kakad, Priyanka P., author Godenschwege, Tanja A., Thesis advisor Florida Atlantic University, Degree grantor Charles E. Schmidt College of Science Department of Biological Sciences |
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| Type of Resource: | text | |
| Genre: | Electronic Thesis Or Dissertation | |
| Date Created: | 2018 | |
| Date Issued: | 2018 | |
| Publisher: | Florida Atlantic University | |
| Place of Publication: | Boca Raton, Fla. | |
| Physical Form: | application/pdf | |
| Extent: | 138 p. | |
| Language(s): | English | |
| Abstract/Description: | L1-type cell adhesion molecule (L1CAM) plays an essential role in the development of nervous system and is also highly relevant for the progression of diseases such as Alzheimer’s disease, stroke and cancers, some of the leading causes of human mortality. In addition to its canonical role as a plasma membrane protein organizing the cytoskeleton, recent in vitro studies have revealed that transmembrane as well as cytosolic fragments of proteolytically cleaved vertebrate L1CAM translocate to the nucleus and regulate expression of genes involved in DNA post-replication repair, cell cycle control, migration and differentiation. However, little is known about the in vivo function of L1CAM in the adult nervous system. This dissertation research focuses on studying in vivo nuclear translocation and function of L1CAM. Using the Drosophila model system, we first show that the sole Drosophila L1CAM homolog, Neuroglian (Nrg), is proteolytically cleaved by Alzheimer’s associated secretases, similar to L1CAM, and is also translocated to the nucleus in the adult nervous system. Subsequently, we have shown that the deletion of highly conserved Ankyrin binding domain or FIGQY motif disrupts nuclear import. Further experiments have revealed that the nuclear translocation of Nrg is in fact regulated by the phosphorylation of the FIGQY motif. Importantly, our studies also show transgenic expression of full-length Nrg or the intracellular domain of Nrg resulted in increased myc expression, which is associated with increased sensitivity to oxidative stress and reduced life span. On the other hand, deletion of the FIGQY motif or mutations preventing its phosphorylation led to decrease in myc expression. In summary, we have identified a novel role for the highly conserved Ankyrin binding domain in nuclear translocation and transcriptional regulation of the Drosophila myc oncogene, which is of high relevance to neurodegenerative diseases and cancer associated with oxidative stress. | |
| Identifier: | FA00013076 (IID) | |
| Degree granted: | Dissertation (Ph.D.)--Florida Atlantic University, 2018. | |
| Collection: | FAU Electronic Theses and Dissertations Collection | |
| Note(s): | Includes bibliography. | |
| Subject(s): |
Cell adhesion molecules. Myc proteins. Transcription, Genetic. Transcription factors Gene expression. Ankyrins. Translocation, Genetic. |
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| Held by: | Florida Atlantic University Libraries | |
| Sublocation: | Digital Library | |
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00013076 | |
| Use and Reproduction: | Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder. | |
| Use and Reproduction: | http://rightsstatements.org/vocab/InC/1.0/ | |
| Host Institution: | FAU | |
| Is Part of Series: | Florida Atlantic University Digital Library Collections. |
