The ubiquitin system forms the major pathway for selective degradation of abnormal, damaged and short-lived proteins in eukaryotes. Ubiquitin becomes attached to substrate proteins to target them for degradation via three types of enzyme: ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2), and ubiquitin protein ligases (E3). E1 enzymes are only necessary to activate ubiquitin and transfer it to an E2 enzyme. Many E2s are present within a eukaryote, and some can ubiquitinate substrates without the aid of an E3 enzyme. Studies in <I>Saccharomyces cerevisiae </I>have shown particular E2s function in processes as diverse as DNA repair, peroxisome biogenesis and cell cycle control. Much of the substrate specificity for ubiquitination is thought to reside within ubiquitin conjugating enzymes. Control of protein levels by selective degradation is important for cell differentiation and developmental processes. To allow specific spatial and temporal distribution of proteins which are key regulators of development, highly selective degradation is required. Ubiquitin-dependent proteolysis also appears essential for developmentally programmed cell death. The experiments in this thesis describe attempts to address the role of the ubiquitin system in development using <I>Drosophila melanogaster </I>as a model system. As ubiquitin conjugating enzymes are thought to each ubiquitinate a subset of proteins, these were the enzymes investigated. Four E2 enzyme genes had previously been cloned in <I>Drosophila, </I>and a further E2 was identified by a polymerase chain reaction screen. The gene was cloned, sequenced and named <I>UbcD4 </I>(ubiquitin conjugating enzyme in <I>D</I><I>rosophila </I>number 4). <I>UbcD4 </I>encodes a protein homologous to bovine E2<SUB>25K</SUB> and yeast UBC1. All five E2 genes were investigated for developmentally regulated transcription. High levels of E2 mRNA were observed in adult females, early embryos and larvae, suggesting specific developmental roles for the ubiquitin system at these stages. Ubiquitination may have a major function in the developing central nervous system, as RNA from all known E2s was found to be abundant in this tissue in embryos.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:653459 |
| Date | January 1996 |
| Creators | Kirby, Ruth |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/11829 |
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