Advisory Committee Chair
Advisory Committee Members
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Unrestricted cell proliferation and suppression of cell death are two essential events for tumor development. My dissertation research involves two proteins, 14-3-3 &tau and EDD which are involved in diverse pathways related to these two fields in recent studies. Previous study demonstrates that 14-3-3ô regulates p21 degradation. Up-regulation of 14-3-3ô is seen in breast cancer and is correlated with the down-regulation of p21 in breast cancer. Amplification or overexpression of EDD was observed in breast cancer and ovarian cancers. Illustrating the new roles of these two proteins in proliferation and cell death will advance our knowledge in tumorigenesis and help us develop right strategies for cancer treatment. Our present study uncovered a new role of EDD in cell cycle progression. Silencing of EDD induces phosphorylation of p53 at Ser15 and the transcription of p53 target genes without activation of DNA damage response. Brdu incorporation assay reveals that depletion of EDD is able to induce the G1/S arrest via p53. On the other hand, overexpression of EDD prevents p53 phosphorylation at Ser15 and the induction of p53 target genes during DNA damage and this effect does not require its E3 ligase activity. We also demonstrated that EDD can directly interact with p53 and the inhibition of p53 phosphorylation by ATM relies on this interaction. Thus, through the association with p53, EDD actively inhibits p53 phosphorylation by ATM, and plays a role in ensuring smooth G1/S progression. As to my second project on 14-3-3ô, we demonstrated that 14-3-3ô regulates the autophagy through Beclin 1, an essential protein in autophagy. We also confirmed that E2Fs regulate Beclin 1 and E2F1 mediated the modulation of Beclin 1 by 14-3-3ô. Futhermore, we revealed that tenascin-C, an anti-adhesive extracellular matrix protein for detachment (a process which causes autophagy), induces Beclin 1 through 14-3-3ô, thus placing the tenascin-C/14-3-3ô/E2F1/Beclin 1 regulation in a physiological context.
Ling, Shiyun, "Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation" (2010). All ETDs from UAB. 2301.