|M.Sc Student||Ben-Ari Inbal|
|Subject||The Role of Ynd1 in the Signal Transduction Pathway Induced|
by Adenovirus E4orf4 Protein in Yeast
|Department||Department of Medicine||Supervisor||Professor Tamar Kleinberger|
|Full Thesis text - in Hebrew|
Adenovirus E4orf4 (early region 4 open reading frame 4) protein induces protein phosphatase 2A-dependent non-classical apoptosis in mammalian cells and irreversible growth arrest in Saccharomyces cerevisiae. Oncogenic transformation sensitizes cells to E4orf4-induced cell death. To uncover additional components of the E4orf4 network required for induction of its unique mode of apoptosis, we used yeast genetics to select gene deletions conferring resistance to E4orf4. Deletion of YND1, encoding a yeast Golgi apyrase, conferred partial resistance to E4orf4. However, Ynd1 apyrase activity was not required for E4orf4-induced toxicity. Ynd1 and Cdc55, the yeast protein phosphatase 2A-B subunit, contributed additively to E4orf4-induced toxicity. Furthermore, concomitant overexpression of one and deletion of the other was detrimental to yeast growth, demonstrating a functional interaction between the two proteins. In addition to their functional interaction, Ynd1 and Cdc55 interacted physically, and this interaction was disrupted by E4orf4, which remained associated with both proteins. The results suggested that Ynd1 and Cdc55 the two E4orf4 partners are balanced, and disruption of this balance by E4orf4 may lead to cell death.