Dynamic interplay between the intermediate filament protein nestin and Cyclin-dependent kinase 5
作者： Hanna-Mari Pallari
DOI:
关键词: Cyclin-dependent kinase 5 、 Molecular biology 、 Nestin 、 Physics
摘要: Cellen har ett s.k. cytoskelett som bl.a. ger stadga at cellen och deltar i dess form- rorelsefunktioner. Intermediarfilamenten ar en viktig del av cytoskelettet de lange varit kanda for sina vasentliga roller att uppratthalla den cellulara organisationen vavnadernas integritet. Pa senare man insett intermediarfilamenten storre funktionell mangsidighet an tidigare tankts sig, med rad olika studier visat betydelsen vid signaleringprocesser. Dessa proteinnatverk samverkar namligen kinaser andra viktiga signalfaktorer darmed cellens signaleringmaskineri. Intermediarfilamentproteinet nestin anvands ofta markor stamceller men fysiologiska funktioner stort sett okanda. Interaktion mellan signalkomplex bestaende cyklin-beroende kinas 5 (eng. Cyclin-dependent kinase, Cdk5) aktivatorprotein p35 upptacktes vart laboratorium fore denna avhandling paborjades. Darfor var syftet min undersoka funktionella regleringen Cdk5/p35 komplexet. Cdk5 multifunktionellt reglerar bade utvecklingen stressreaktioner nerver muskler. Vi visade skyddar neuronala under oxidativ stress genom formaga hamma Cdk5s skadliga aktivitet. Genom forankra komplexet, subcellulara lokaliseringen minskar klyvningen till mer stabila aktivatorn p25. Vi demonstrerade ocksa aktiveringsmekanismen differentiering muskelceller. Proteinkinas C zeta (PKCzeta) avslojades ha accelera p25, oka aktiviteten hos Cdk5. Nestin kunde sin reglera signalkomplexet styra muskelcellernas differentiering. Denna doktorsavhandling pa avgorande vis okat forstaelsen reglerande mekanismer styr aktivering. Avhandling presenterar PKCzeta kritiska faktorer reglering. Vidare innehaller avhandlingen ny information om funktionerna vi vara reglerare cellernas overlevnad
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