Identification and Characterization of a New E1 that Activates Ubiquitin and FAT10

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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.identifier.other 760078299 en
dc.identifier.uri http : / /hdl .handle .net /2152 .5 /284 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.medium Electronic en
dc.format.mimetype application /pdf 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.degree.name Doctor of Philosophy en
thesis.degree.level Ph .D . en
thesis.degree.discipline Genetics & Development en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.department en
dc.format.digitalOrigin born digital en
thesis.date.available 2009 -05 -13 en

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Identification and Characterization of a New E1 that Activates Ubiquitin and FAT10. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /284 .

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