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https://scholarbank.nus.edu.sg/handle/10635/196070
DC Field | Value | |
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dc.title | CELL SURFACE NUCLEOLIN MEDIATES ADAMTS5- INDUCED APOPTOSIS IN ENDOTHELIAL CELLS | |
dc.contributor.author | DOGAN CAN KIRMAN | |
dc.date.accessioned | 2021-08-07T18:00:25Z | |
dc.date.available | 2021-08-07T18:00:25Z | |
dc.date.issued | 2021-01-21 | |
dc.identifier.citation | DOGAN CAN KIRMAN (2021-01-21). CELL SURFACE NUCLEOLIN MEDIATES ADAMTS5- INDUCED APOPTOSIS IN ENDOTHELIAL CELLS. ScholarBank@NUS Repository. | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/196070 | |
dc.description.abstract | A Disintegrin and Metalloproteinase with ThromboSpondin motif 5 (ADAMTS5), was previously identified by our lab as an anti-angiogenic/tumorigenic protein. Similarly, the autocatalytically cleaved truncate of ADAMTS5 (TS5-p45) inhibits angiogenesis and induces endothelial cell (EC) apoptosis. However, how ADAMTS5 triggers EC apoptosis remains unclear. In this work, I identified that EC surface nucleolin (NCL) is a novel high-affinity receptor for ADAMTS5. Upon interacting with surface NCL, TS5-p45 is internalized through clathrin- and caveolin-dependent endocytosis and trafficked to the nucleus via intact late endosomes (LEs). LE-mediated nuclear trafficking is required for TS5-p45-induced apoptosis. I also demonstrated that cell surface NCL shuttles extracellular TS5-p45 to the nucleus via nuclear import mechanism. Furthermore, I identified a set of apoptosis-related genes that might be involved in TS5-p45-induced apoptosis. This work identifies the critical role of cell surface NCL-mediated nuclear trafficking for ADAMTS5-induced EC apoptosis. Hence, ADAMTS5 can be used in NCL-targeted anti-angiogenic/tumorigenic therapy. | |
dc.language.iso | en | |
dc.subject | ADAMTS5, nucleolin, apoptosis, nuclear trafficking, anti-angiogenesis | |
dc.type | Thesis | |
dc.contributor.department | BIOLOGICAL SCIENCES | |
dc.contributor.supervisor | Ruowen Ge | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY (FOS) | |
dc.identifier.orcid | 0000-0002-3767-7096 | |
Appears in Collections: | Ph.D Theses (Open) |
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KirmanDC.pdf | 6.66 MB | Adobe PDF | OPEN | None | View/Download |
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