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Tyrosine kinase를 경유한 ERK1/2의 활성화로 인한 TRAIL에 의해 유발된 HeLa 세포자멸사시 세포보호작용

The activation of ERK1/2 via tryosine kinase pathway attenuates TRAIL-induced apoptosis in HeLa cell

김성수|이명우|강용구|정윤희|박순철|김경용|이도연|김대성|이원복|손동섭|김석원|노유헌
대한체질인류학회|2004.09|해부·생물인류학 (Anatomy & Biological Anthropology)|제17권 제3호|pp. 187-196|DOI 10.11637/aba.2004.17.3.187

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키워드

세포자멸사ERK1/2TRAILtyrosine kinaseBcl-2 proteinTyrosine kinaseApoptosis.
주제분류해부학

초록

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)는 암세포에서 세포자멸사를 유발시키는 세포외 신호전달을 가져오는 물질이다. TRAIL에 의한 세포자멸사 신호전달 체계를 규명하기 위하여 우리는 HeLa 세포를 사용해서 세포자멸사에서 ERK1/2의 역할을 알아보았다. 이 연구에서 우리는 TRAIL이 tyrosine kinase를 통해서 ERK1/2가 활성화 된다는 것을 밝혔다. 이것이 세포자멸사를 막아주는 Bcl-2 단백질의 양을 늘린다. Tyrosine kianse의 억제제인 genistein은 매우 극적으로 ERK1/2의 활성화정도를 막으며 또한 세포사멸도 증가시킨다. 더욱이 PD98059를 이용한 ERK1/2의 활성화를 억제한 결과 ERK1/2의 활성화와 Bcl-2 단백질의 양이 줄어듦을 통해서 세포자멸사가 증가되었다. 결과적으로 우리의 연구는 tryrosine kinase를 경유한 ERK1/2의 활성화가 TRAIL에 의한 세포자멸사 과정중에 Bcl-2의 양을 증가시킴으로서 세포내 방어 시스템의 세포보호 작용을 하게 된다는 것을 보여준 것이라 하겠다.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves as an extracellular signal triggering apoptosis in tumor cells. To characterize the molecular events involved in TRAIL-induced apoptotic signaling, we investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in the apoptosis using HeLa cells. Here we show that TRAIL pronounced ERK1/2 activation through a tyrosine kinase-dependent mechanism, subsequently elevated anti-apoptotic Bcl-2 protein levels. Pretreatment with Genistein, an inhibitor of tyrosine kinase, significantly attenuated ERK1/2 activation and enhanced cell death. Moreover, inhibition of ERK1/2 with PD98059 promoted apoptotic cell death through the down-regulation of ERK1/2 activity and Bcl-2 protein levels. Taken together, our results suggest that the activation of ERK1/2 via tyrosine kinase pathway plays a protective role as the mechanism of cellular defense through the up-regulation of Bcl-2 protein levels in TRAIL-induced apoptosis.

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