E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development 英文参考文献.docVIP

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E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development 英文参考文献.doc

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E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development 英文参考文献

E1Ubiquitin-ActivatingEnzymeUBA-1PlaysMultiple RolesthroughoutC.elegansDevelopment MadhuraKulkarni1,HaroldE.Smith2* 1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, United States of America, 2Center for Advanced Research in Biotechnology,UniversityofMarylandBiotechnologyInstitute,Rockville,Maryland,UnitedStatesofAmerica Abstract Poly-ubiquitinationoftargetproteinstypically marksthemfordestructionvia theproteasomeandprovidesanessential mechanism for the dynamic control of protein levels. The E1 ubiquitin-activating enzyme lies at the apex of the ubiquitinationcascade,anditsactivityisnecessaryforallsubsequentstepsinthereaction.Wehaveisolatedatemperature- sensitive mutation in the Caenorhabditis elegans uba-1 gene, which encodes the sole E1 enzyme in this organism. ManipulationofUBA-1activityatdifferentdevelopmentalstagesrevealsavarietyoffunctionsforubiquitination,including novel roles in sperm fertility, control of body size, and sex-specific development. Levels of ubiquitin conjugates are substantially reduced in the mutant, consistent with reduced E1 activity. The uba-1 mutation causes delays in meiotic progression in the early embryo, a process that is known to be regulated by ubiquitin-mediated proteolysis. The uba-1 mutationalsodemonstratessyntheticlethalinteractionswithallelesoftheanaphase-promotingcomplex,anE3ubiquitin ligase.Theuba-1mutationprovidesasensitizedgeneticbackgroundforidentifyingnewinvivofunctionsfordownstream componentsoftheubiquitinenzymecascade,anditisoneofthefirstconditionalmutationsreportedfortheessentialE1 enzymeinametazoananimalmodel. Citation: Kulkarni M, Smith HE (2008) E1 Ubiquitin-Activating Enzyme UBA-1 Plays Multiple Roles throughout C. elegans Development. PLoS Genet 4(7): e1000131.doi:10.1371/journal.pgen.1000131 Editor:MaryMullins,UniversityofPennsylvaniaSchoolofMedicine,UnitedStatesofAmerica ReceivedFebruary13,2008;AcceptedJune18,2008;PublishedJuly18,2008 Copyright: ? 2008 Ku