Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/113280
DC Field | Value | |
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dc.title | CHARACTERIZATION OF THE ROLE OF K63-LINKED UBIQUITINATION IN PROTEIN AND MITOCHONDRIAL HOMEOSTASIS: IMPLICATIONS FOR PARKINSON'S DISEASE | |
dc.contributor.author | LIM GUI YIN GRACE | |
dc.date.accessioned | 2014-11-30T18:00:37Z | |
dc.date.available | 2014-11-30T18:00:37Z | |
dc.date.issued | 2014-03-31 | |
dc.identifier.citation | LIM GUI YIN GRACE (2014-03-31). CHARACTERIZATION OF THE ROLE OF K63-LINKED UBIQUITINATION IN PROTEIN AND MITOCHONDRIAL HOMEOSTASIS: IMPLICATIONS FOR PARKINSON'S DISEASE. ScholarBank@NUS Repository. | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/113280 | |
dc.description.abstract | Poly-ubiquitin modification usually targets proteins for proteasomal degradation. However, K63-linked chain is atypical as it is uncoupled from the proteasome. Here, I sought to clarify the role of this non-canonical form of ubiquitination in protein and mitochondrial homeostasis. I showed that during proteasome dysfunction, K63-polyubiquitination is enhanced and parkin is a key enzyme involved. Mechanistically, the phenomenon occurs as a result of increased affinity of parkin for Ubc13 (an E2 that mediates K63-polyubiquitination exclusively), which appears to facilitate the autophagic clearance of substrates and as such promotes cellular survival in times of proteolytic stress. Separately, I showed that K63-polyubiquitination can participate in mitochondrial homeostasis by regulating the expression of a cleaved form of PINK1 which is otherwise rapidly degraded. I have also identified the pathway involved in this. Taken together, my study has expanded the role of K63-polyubiquitination to include its participation in protein and mitochondrial homeostasis. | |
dc.language.iso | en | |
dc.subject | K63-linked ubiquitination, parkin, PINK1, Parkinson's disease, protein homeostasis, mitochondrial homeostasis | |
dc.type | Thesis | |
dc.contributor.department | PHYSIOLOGY | |
dc.contributor.supervisor | LIM KAH LEONG | |
dc.contributor.supervisor | SOONG TUCK WAH | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY | |
dc.identifier.isiut | NOT_IN_WOS | |
Appears in Collections: | Ph.D Theses (Open) |
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