Role of Individual Subunits of the Neurospora crassa CSN Complex in Regulation of Deneddylation and Stability of Cullin Proteins 英文参考文献.docVIP
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Role of Individual Subunits of the Neurospora crassa CSN Complex in Regulation of Deneddylation and Stability of Cullin Proteins 英文参考文献
RoleofIndividualSubunitsoftheNeurosporacrassaCSN
ComplexinRegulationofDeneddylationandStabilityof
CullinProteins
JiyongWang1,QiwenHu1,HuijieChen1,ZhipengZhou1,WeihuaLi2,YingWang1,ShaojieLi3*,QunHe1*
1StateKeyLaboratoryofAgrobiotechnology,CollegeofBiologicalSciences,ChinaAgriculturalUniversity,Beijing,China,2InstituteofBasicMedicalSciences,National
CenterofBiomedicalAnalysis,Beijing,China,3KeyLaboratoryofSystematicMycologyandLichenology,InstituteofMicrobiology,ChineseAcademyofSciences,Beijing,
China
Abstract
The Cop9 signalosome (CSN) is an evolutionarily conserved multifunctional complex that controls ubiquitin-dependent
proteindegradationineukaryotes.WefoundsevenCSNsubunitsinNeurosporacrassainapreviousstudy,butonlyone
subunit,CSN-2,wasfunctionallycharacterized.Inthisstudy,wecreatedknockoutmutantsfortheremainingindividualCSN
subunitsinN.crassa.Byphenotypicobservation,wefoundthatlossofCSN-1,CSN-2,CSN-4,CSN-5,CSN-6,orCSN-7resulted
inseveredefectsingrowth,conidiation,andcircadianrhythm;thedefectseveritywasgene-dependent.Unexpectedly,CSN-
3knockoutmutantsdisplayedthesamephenotypeaswild-typeN.crassa.Consistentwiththesephenotypicobservations,
deneddylation of cullin proteins in csn-1, csn-2, csn-4, csn-5, csn-6, or csn-7 mutants was dramatically impaired, while
deletionofcsn-3didnotcauseanyalterationintheneddylation/deneddylationstateofcullins.Wefurtherdemonstrated
thatCSN-1,CSN-2,CSN-4,CSN-5,CSN-6,andCSN-7,butnotCSN-3,wereessentialformaintainingthestabilityofCul1inSCF
complexesandCul3andBTBproteinsinCul3-BTBE3s,whilefiveoftheCSNsubunits,butnotCSN-3andCSN-5,werealso
requiredformaintainingthestabilityofSKP-1inSCFcomplexes.AllsevenCSNsubunitswerenecessaryformaintainingthe
stabilityofCul4-DDB1complexes.Inaddition,CSN-3wasalsorequiredformaintainingthestabilityoftheCSN-2subunit
andFWD-1intheSCFFWD-1 complex.Together,theseresultsnotonlyprovidefunctionalinsightsintothedifferentrolesof
individualsubunitsintheCSNcomplex,butalsoestablishafunctionalframeworkforunderstandingthemul
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