The Role of the Skp2-CyclinA Interaction in Drosophila Cell Cycle Regulation
Type of Proposal
Oral presentation
Faculty
Faculty of Science
Faculty Sponsor
Andrew Swan
Proposal
The cell cycle is a highly controlled process, requiring the role of several regulatory proteins to ensure proper cell division. One of these proteins is Skp2, a substrate recognition subunit of the SCF complex - a protein conglomerate required for the destruction of the tumour suppressor, p27/Dap. This role has long characterized Skp2 as a proto-oncogene, with the potential to interfere with normal cell regulation if overexpressed; however, Skp2 is also necessary for proper cell division, as the loss of Skp2 results in polyploidy of mitotically dividing cells. While most research on Skp2 has emphasized its role down-regulating p27, one study indicates that the knockdown of Skp2 might have an effect on other cell cycle regulators in a pathway independent of p27, causing polyploidy. However, these regulators that Skp2 affects, have not yet been fully clarified. Among important cell cycle regulators Skp2 interacts with is Cyclin A, a key protein in G2 regulation and mitotic entry in Drosophila. Like Skp2, Cyclin A is required for preventing polyploidy, indicating that Cyclin A is a point of interest in our study of Skp2. Moreover, previous studies show that the N-terminus of Skp2 interacts directly with Cyclin A in both Drosophila and mammals via a domain independent of SCF interaction; the N-terminus also happens to be required for rescuing polyploidy in Skp2 null mitotic cells. Thus, we predict that it is the Skp2-CycA interaction that is necessary for preventing polyploidy. To test this prediction, this project will aim to characterize the Skp2-CycA interaction in a Drosophila model through various immunochemistry techniques. Understanding this interaction in greater detail will enhance our knowledge of the cellular processes that are crucial for cell cycle regulation.
Start Date
31-3-2017 3:30 PM
End Date
31-3-2017 4:50 PM
The Role of the Skp2-CyclinA Interaction in Drosophila Cell Cycle Regulation
The cell cycle is a highly controlled process, requiring the role of several regulatory proteins to ensure proper cell division. One of these proteins is Skp2, a substrate recognition subunit of the SCF complex - a protein conglomerate required for the destruction of the tumour suppressor, p27/Dap. This role has long characterized Skp2 as a proto-oncogene, with the potential to interfere with normal cell regulation if overexpressed; however, Skp2 is also necessary for proper cell division, as the loss of Skp2 results in polyploidy of mitotically dividing cells. While most research on Skp2 has emphasized its role down-regulating p27, one study indicates that the knockdown of Skp2 might have an effect on other cell cycle regulators in a pathway independent of p27, causing polyploidy. However, these regulators that Skp2 affects, have not yet been fully clarified. Among important cell cycle regulators Skp2 interacts with is Cyclin A, a key protein in G2 regulation and mitotic entry in Drosophila. Like Skp2, Cyclin A is required for preventing polyploidy, indicating that Cyclin A is a point of interest in our study of Skp2. Moreover, previous studies show that the N-terminus of Skp2 interacts directly with Cyclin A in both Drosophila and mammals via a domain independent of SCF interaction; the N-terminus also happens to be required for rescuing polyploidy in Skp2 null mitotic cells. Thus, we predict that it is the Skp2-CycA interaction that is necessary for preventing polyploidy. To test this prediction, this project will aim to characterize the Skp2-CycA interaction in a Drosophila model through various immunochemistry techniques. Understanding this interaction in greater detail will enhance our knowledge of the cellular processes that are crucial for cell cycle regulation.