{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/284"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/284","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Identification and Characterization of a New E1 That Activates Ubiquitin and FAT10","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Chiu, Yu-Hsin"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Chen, Zhijian J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T17:26:00Z","date_published":"2010-07-12T17:26:00Z","updated_at":"2026-07-24T05:52:11Z","subjects":["Ubiquitin","Tumor Necrosis Factor-alpha","Ubiquitin-Activating Enzymes"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["760078299"],"render_values":[{"text":"760078299","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/284","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Zhijian J."]},{"key":"dc:creator","label":"Author","values":["Chiu, Yu-Hsin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07-12T17:26:00Z","2008-05-13"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text","dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Ubiquitin","Tumor Necrosis Factor-alpha","Ubiquitin-Activating Enzymes"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/284","760078299"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Identification and Characterization of a New E1 That Activates Ubiquitin and FAT10"]}]}],"canonical_facts":{"dc:contributor":["Chen, Zhijian J."],"dc:creator":["Chiu, Yu-Hsin"],"dc:date":["2010-07-12T17:26:00Z","2008-05-13"],"dc:description":["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."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/284","760078299"],"dc:language":["en"],"dc:subject":["Ubiquitin","Tumor Necrosis Factor-alpha","Ubiquitin-Activating Enzymes"],"dc:title":["Identification and Characterization of a New E1 That Activates Ubiquitin and FAT10"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:11Z"}