A Genetic Screen for Tribbles Suppressors Identifies the E3 Ubiquitin Ligase Neuralized as a Novel Target
No Thumbnail Available
Authors
Meeting name
Sponsors
Date
Journal Title
Format
Thesis
Subject
Abstract
In this dissertation, I used the Drosophila wing as a model tissue for a genetic screen to identify novel targets of Tribbles. Drosophila Tribbles is the founding member of a family of pseudokinases conserved between metazoans. Tribbles family proteins have roles in the cell cycle, insulin signaling, tissue growth and early development, and have been associated with a myriad of human diseases. In the wing, expression of tribbles by the engrailed-GAL4 driver generates a distinct visual phenotype; larger cells in the posterior of the wing and overall smaller tissue size. Co-misexpression of the known targets of Tribbles slbo (Slow Border Cells) and string suppresses the Tribbles wing phenotype. We used this observation as a tool to screen for additional Tribbles targets and from our screen we identified three E3 Ubiquitin ligases as novel interactors; Neuralized, Mindbomb1 and Parkin. Of the targets identified from the screen, we focused on Neuralized. We found that Tribbles physically bound to Neuralized in a yeast two hybrid assay and in vivo, Tribbles co misexpression in an ovarian model epithelium, the follicle cells, stabilized a tagged version of Neuralized. Neuralized has known roles in Notch signaling, and so we hypothesized that Tribbles promotes Notch signaling in the follicle cells and consistent with this, we found that both Tribbles and Neuralized turn on expression of Eyes Absent, a marker of stretch cell flattening activated by Neuralized-mediated Notch signaling.
Table of Contents
Introduction -- A screen for novel TRBL interactors identifies E3 ubiquinti ligases as candidate interactors -- TRBL stabilizers neur to block its activity -- A drosophila model of insulin resistance associated with the human TRIB3 q/r polymorphism -- Fijiwings polarity: an open source toolkit for semi-automated detection of cell polarity -- Future directions -- Appendix
DOI
PubMed ID
Degree
Ph.D.