Identification and Characterization of a New E1 that Activates Ubiquitin and FAT10
| dc.contributor.advisor | Chen, Zhijian J. | en |
| dc.creator | Chiu, Yu-Hsin | en |
| dc.date.accessioned | 2010-07-12T17:26:00Z | en |
| dc.date.accessioned | 2014-02-19T22:01:02Z | |
| dc.date.available | 2010-07-12T17:26:00Z | en |
| dc.date.available | 2014-02-19T22:01:02Z | |
| dc.date.issued | 2008-05-13 | en |
| dc.description.abstract | Ubiquitination is one of many post-translational modifications in eukaryotes. Three enzymes (E1, E2, and E3) are involved in conjugating ubiquitin to protein substrates. I identified a novel E1-like protein, E1-L2, which is homologous to the ubiquitin E1 and another E1 involved in the activation of the ubiquitin-like protein ISG-15 (E1-L1). E1-L2 activates both ubiquitin and FAT10, a ubiquitin-like protein. Interestingly, E1-L2 can transfer ubiquitin to only a subset of E2 enzymes, Ubc5 and Ubc13, but not Ubc3 and E2-25K, suggesting that E1-L2 may function in certain ubiquitination reactions. E1-L2, but not E1 or E1-L1, forms a thioester with FAT10 in vitro. The formation of the thioester bond requires the active site cysteine residue of E1-L2 and the C-terminal diglycine motif of FAT10. In addition, endogenous FAT10 forms a thioester with E1-L2 in cells stimulated with tumor necrosis factor-alpha and interferon-gamma, which induce FAT10 expression. Silencing of E1-L2 expression by RNAi impaired the formation of FAT10 conjugates in cells. Furthermore, E1-L2 deficient embryos died before embryonic day 13.5, suggesting that E1-L2 is essential for early embryonic development. Since the FAT10-deficient mice develop normally, it is likely that specific ubiquitination reactions catalyzed by E1-L2 play an important role in animal development. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.other | 760078299 | en |
| dc.identifier.uri | http://hdl.handle.net/2152.5/284 | en |
| dc.language.iso | en | en |
| dc.subject | Ubiquitin | en |
| dc.subject | Tumor Necrosis Factor-alpha | en |
| dc.subject | Ubiquitin-Activating Enzymes | en |
| dc.title | Identification and Characterization of a New E1 that Activates Ubiquitin and FAT10 | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.date.available | 2009-05-13 | en |
| thesis.degree.department | en | |
| thesis.degree.discipline | Genetics & Development | en |
| thesis.degree.grantor | Graduate School of Biomedical Sciences | en |
| thesis.degree.level | Ph.D. | en |
| thesis.degree.name | Doctor of Philosophy | en |