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Title: Studies on the autophagy gene WIPI4 and its interactor UBR5
Author: Zhu, Ye
ISNI:       0000 0004 8500 4958
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2020
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Autophagy is a tightly regulated process that sequesters and delivers proteins and other cellular substances for degradation in the lysosome. Dysfunction of autophagy has been implicated in many diseases including neurodegenerative diseases, cancer, and infectious diseases. Beta-propeller Protein-Associated Neurodegeneration (BPAN), an early onset neurodegenerative disease, is caused by mutations in WIPI4, a member of the WD repeat domain phosphoinositide-interacting family. This thesis identifies WIPI4 as a regulator of the closure of autophagosomes. Although many proteins have been found to indirectly regulate autophagosome closure, the exact mechanism of this process has remained unclear. This thesis explored the regulatory mechanism of GABARAP by WIPI4. GABARAP is a potential closure regulator and is also required for expansion and fusion steps of autophagy. I identified that WIPI4 regulates the stability and trafficking of GABARAP. Altogether, this thesis furthers the understanding of the mechanism of autophagosome closure.
Supervisor: Rubinsztein, David Sponsor: China Scholarship Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: autophagy ; proteasome ; neurodegeneration disease