고찰

키게 된다 (MinhasKM etal.,2003).또한 SemuelF 등은 KT-MT attachment

향후 RSK2가 직접적으로 microtubulestability에 관여 하는지 아니면 RSK2 의 알려지지 않은 다른 기질을 통해서 microtubule stability에 관여 하여 KT-MT attachment에 관여하는지 해당 관련 실험의 진행이 이에 대한 우리의 이해를 깊게 할 것이다.

Ⅴ.결 론

본 연구는 Ras/MAP Kinase신호전달계의 하위 매개체인 RSK2의 과발현에 의해 유전체 불안정성을 유도하는지 알고자 하였고,유전체 불안정성이 일어난다 면 그 원인이 무엇인지 알고자 하였다.본 연구에서 지속적인 활성을 나타내는 RSK2가 유전체 불안정성을 일으키는 것을 확인 할 수 있었으며 지속적으로 활 성을 나타내는 RSK2가 SAC defects와 kinetochore-microtubule (KT-MT) attachmentdefects에 영향을 주어 유전체 불안정성을 유도하는 것으로 관찰 되 었다. 구체적으로 RSK2의 과활성화에 따른 kinetochore-microtubule의 hyper-stability가 유전체 불안정성을 유발함을 확인하였다.이 결과는 이미 보고 된 Ras/Mitogen-activated protein kinase(MAPK)신호전달체계가 유전체 불안 정성에 관계가 있다는 사실을 뒷받침하는 것이며,특히 MAP Kinase신호전달체 계에서 일어나는 암의 발생과 진행에 있어서 유전체 불안정성이 연관되어 있다 는 보고들을 비추어 볼 때,RSK2와 고형종양의 특징인 유전체 불안정성의 관계 에 대해 처음으로 밝혔다고 할 수 있다.

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ABSTRACT

-Const i t ut i vel y act i ve-RSK2i nduceschr omosomal i nst abi l i t y t hr ough di ver semechani sms

Weobserved thatconstitutively acvtiveRSK2 induced chromosomal instability such as lagging chromosome and chromosome bridge, micro-nucleus and abnormalnumberofchromosome.Mechanism study revealed thatconstitutively activeRSK2induced chromosomalinstability

through spindleassembly checkpointdefectsand kinetochore-microtubule (KT-MT)attachmentdefects.SinceRSK2localizesin microtubuleduring mitosis,wefocusedon therelationshipbetweenRSK2andmicrotubule.We analyzedkinetochore-microtubule(KT-MT)attachmentdynamicsthroughcold stableassay and nocodazolesensitivity assay.Interestingly,theseresults indicate thatconstitutively active RSK2 enhanced the stability of microtubules.Inaddition,weobservedthattheco-transfectionofRSK2and MCAK decreased lagging chromosomeand chromosome bridgeduring anaphase,indicating thatenhancementofkinetochoremicrotubulestability wasindeedthecauseofCIN in thesecells.Taken together,constitutively activeRSK2inducedchromosomalinstabilitythroughincreaseinthestability ofmicrotubules.YetunidentifiedeffectofRSK2activation in SAC activity also seemsto affectCIN.Wehereby providea possiblenew insighton therole ofRSK2 activation in cancerformation as wellas to cancer progression.

Keywords:RSK2,chromosomalinstability(CIN),microtubule