PRMT5通過調(diào)節(jié)高爾基體組裝控制細(xì)胞的生長.pdf

1、蘭州大學(xué)碩士學(xué)位論文PRMT5通過調(diào)節(jié)高爾基體組裝控制細(xì)胞的生長姓名：周忠衛(wèi)申請(qǐng)學(xué)位級(jí)別：碩士專業(yè)：生物化學(xué)與分子生物學(xué)指導(dǎo)教師：曹儀植鮑時(shí)來20050501蘭型查蘭堡主翌塑生堂竺絲壅!!堅(jiān)!望塾塑堇壹塑薹笪塑!墮型塑絲!!蘭堡PRMT5RegulatesCellProliferationbyControllingtheAssemblyofGolgiAbstractProteinargininemethylatransferases(P

2、RMTs)catalyzetotransferthemethylgroupsfromSadenosylmethionine(S川)toanarginineresidue。TwoclassesofPR岍shavebeenidentifiedandclassifledbasedOilthesymmetryoftheirreactionproductsineukaryoticeells。TypeIPRm‘scataIyzetoformmono

3、—andasymmetricdimethylatedarginine，whiletypeIIenzymemethylatesarginineresiduestoformmonoandsymmetricdimethylatedarginine。Inmammals，fiveoftypeIenzymes(PRMTl，一2，一3。一4，and一6)andtwooftypeIIPRMTs，PRMT5andPR酣T7havebeenidentifl

4、ed。P黜fr5(alsoknownasSkbl，Hsl7，andJBPl)wasfirstisolatedbyatwo—hybridscreenforbindingproteinsofproteinkinaseShkl，thep21一activatedkinase(PAK)homologasapositivemodulatorofShklinfissionyeast。如vivoSkblinteractswitharegionofthe

5、NterminalregulatorydomainofShkldistinctfromthattowhichCdc42binds，andthatShkl，Cdc42，andSkblareabletoformaternarycomplexrequiredforcellviability，normalmorphology。Inmammalian，activatedCdc42HsrecuitesanovelmemberofthePAKfami

6、Iy—1PAl(4totheGolgiapparatusandplayaroleintheGolgimorphogenesisandproteintransportthrougheffecttheactinrearrangement。Buttherehaven’tanyreportabouttheroleofPRMT5inGolgi。PRMT5wasdemonstratedastypeIIproteinargininemethyltra

7、nsferase。MountingevidencehasshownthatPRMT5mightbeaveryimportantcomponenttegulateawidevarietyofsignalingcascadesincludingassemblyofUsnRNPs，transcriptionalelongation，hSWI／SNFchromatinremodelingcomplex，andassociationwiththe

8、promotorregionofcYCLINEandCAD。RecentworkhasshownthatHsl7theP黜肛5homologueinXenopuslaevisisacomponentoftheDNAreplicationcheckpoint。EarlyandrecentworkhaveshownthatPRMT5directregulateshistonemodificationinvitroandinvivo。Howe

9、ver，theroleofPRMT5incontrollingcellgrowthandproliferationremainsobscure。Inthiswork，weinvestigatedthesubcellularlocationsofPRm‘5andtheroleofPRMT5intheGolgiandcontrollingthecellgrowthandproliferation。OurresultsshowPRlIIT5s