Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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Mutual Activities of IEX-1 and MCL-1 on the Apoptosis of Ovarian Cancer Cells

난소암 세포에서 IEX-1과 MCL-1 단백질들의 세포 사멸 기능에 관한 상호작용

  • Yoon, Seong-Min (Dept. of Biomedical Science, College of Life Science, CHA University) ;
  • Na, Soon-Young (Dept. of Biomedical Science, College of Life Science, CHA University) ;
  • Kim, Hong-Man (Dept. of Life Science, College of Natural Science, Chung-Ang University) ;
  • Lee, Kang-Seok (Dept. of Life Science, College of Natural Science, Chung-Ang University) ;
  • Bae, Jee-Hyeon (Dept. of Biomedical Science, College of Life Science, CHA University)
  • 윤성민 (CHA 의과학대학교 생명과학대학 의생명과학과) ;
  • 나순영 (CHA 의과학대학교 생명과학대학 의생명과학과) ;
  • 김홍만 (중앙대학교 자연과학대학 생명과학과) ;
  • 이강석 (중앙대학교 자연과학대학 생명과학과) ;
  • 배지현 (CHA 의과학대학교 생명과학대학 의생명과학과)
  • Received : 2010.03.08
  • Accepted : 2010.04.28
  • Published : 2010.06.30
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Abstract

Apoptosis is a crucial mechanism for the proper regulation of homeostasis. BCL-2 family proteins are key molecules which control cellular survival and apoptosis. MCL-1 (myeloid cell leukemia-1) is a pro-survival member of BCL-2 family that promotes the survival of cells, and is highly expressed in diverse cancers including ovarian cancer, leukemia, and cervical cancer. Previously we identified IEX-1 (immediate early response gene X-1) as a binding partner of MCL-1. In the present study, we demonstrated that overexpression of IEX-1 induced apoptosis of ovarian cancer cells. Moreover, IEX-1 significantly attenuated the pro-survival function of MCL-1 in these cells. Also, IEX-1-induced cell death activity was able to be modulated by changes in the expression level of MCL-1. Thus, these results suggest that both IEX-1 and MCL-1 modulate each other's function controlling cellular survival and death and the inhibitory activity of IEX-1 toward MCL-1 may be applied for the development of chemotherapeutics.

세포 사멸(apoptosis)은 세포의 항상성을 적절하게 유지하기 위한 중요한 메커니즘이다. BCL-2 family 단백질들은 세포의 생존과 세포 사멸을 조절하는 중요한 단백질이다. MCL-1 단백질은 세포의 생존을 촉진시키는 기능을 하는 pro-survival BCL-2 family member이며, 난소암, 혈액암, 자궁 경부암과 같은 다양한 암 조직에서 높게 발현하고 있다. 이전 연구에서, 본 연구진에 의해서 IEX-1 단백질은 MCL-1의 결합 단백질로 밝혀졌다. 본 연구에서는, 난소암 세포에서 IEX-1의 과다 발현에 의한 세포 사멸이 유도되는 것을 밝혔다. 더욱이, IEX-1 단백질은 MCL-1 단백질의 세포 생존을 위한 기능을 감소시켰으며, IEX-1에 의한 세포 사멸 효과는 MCL-1의 발현 정도의 변화에 의해서 그 기능이 영향을 받고 있었다. 그러므로 이러한 결과들은 IEX-1과 MCL-1은 세포 사멸과 생존을 조절하는 서로의 기능에 영향을 미치고, MCL-1의 기능에 대한 IEX-1의 세포 생존율 억제 효과는 항암치료 방법의 개발에 응용될 수 있는 가능성을 제시해 준다.

Keywords

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