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Title: | CELL SURFACE NUCLEOLIN MEDIATES ADAMTS5- INDUCED APOPTOSIS IN ENDOTHELIAL CELLS | Authors: | DOGAN CAN KIRMAN | ORCID iD: | orcid.org/0000-0002-3767-7096 | Keywords: | ADAMTS5, nucleolin, apoptosis, nuclear trafficking, anti-angiogenesis | Issue Date: | 21-Jan-2021 | Citation: | DOGAN CAN KIRMAN (2021-01-21). CELL SURFACE NUCLEOLIN MEDIATES ADAMTS5- INDUCED APOPTOSIS IN ENDOTHELIAL CELLS. ScholarBank@NUS Repository. | 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. | URI: | https://scholarbank.nus.edu.sg/handle/10635/196070 |
Appears in Collections: | Ph.D Theses (Open) |
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