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[국내논문] Ras GTPase 및 Ras GTPase activating protein과 사람의 질병
Ras GTPases and Ras GTPase Activating Proteins (RasGAPs) in Human Disease 원문보기

생명과학회지 = Journal of life science, v.28 no.9 = no.221, 2018년, pp.1100 - 1117  

장종수 (대진대학교 생명화학부)

초록
AI-Helper 아이콘AI-Helper

Ras superfamily에 속하는 monomeric small GTPase는 현재까지 170여 종이 알려져 있으며 이들은 세포 신호전달에 있어서 분자 스위치(molecular switch)로 작용하고 있다. Ras GTPase는 guanosine diphosphate (GDP)와 결합하여 불활성화 되거나 혹은 guanosine triphosphate (GTP)와 결합하여 활성화되는 guanosine nucleotide 결합단백질로서 세포내의 수많은 생리작용을 조절하고 있다. 즉, 쉬고 있던 불활성화 상태의 Ras-GDP는 외부 신호에 반응하여 활성화 된 guanine nucleotide exchange factor (GEF)에 의하여 활성형인 Ras-GTP상태로 전환되어 그 하류로 신호를 전달하는 효과기로 작용하게 된다. 신호전달을 마친 Ras-GTP는 다시 불활성형인 Ras-GDP로 전환되어야 하는데 Ras 자체의 GTPase 활성이 미약하여 RasGTPase activating protein (RasGAP)의 도움을 받아야만 한다. 이와 같이 Ras GTPase는 GEF와 GAP의 활성으로 세포 안의 스위치를 켜고 끄게 된다. 현재까지 알려진 인간 암(cancer)의 30% 이상이 돌연변이를 포함하는 Ras switch의 비정상적인 작동에 기인한다는 점이 밝혀져 있으므로 Ras GTPase의 구조와 생리적 기능에 대한 최근의 연구결과들을 요약하였다. 나아가 GTPase activating protein으로서의 기능을 상실한 RasGAP분자의 돌연변이는 세포 안의 Ras 스위치를 계속 켜 두는 상태인 Ras-GTP 상태를 유발함으로서 종국에는 암의 발생을 촉발하게 된다. 이에, 본고에서는 최근에 와서 tumor suppressor로서 알려지면서 암의 치료 표적단백질로 떠오르게 된 RasGAP의 인체생리학적 기능을 고찰하였다. 인간 게놈 안에는 RASA1, NF1, GAP1 family 및 SynGAP family 등에 속하는 14종의 RasGAP 분자들이 존재하는데 이들 GAP분자들의 이상과 인간 질병의 연관성에 대한 최근의 연구결과들에 대해 고찰하였다.

Abstract AI-Helper 아이콘AI-Helper

The Ras superfamily of small G-proteins acts as a molecular switch on the intracellular signaling pathway. Upon ligand stimulation, inactive GTPases (Ras-GDP) are activated (Ras-GTP) using guanine nucleotide exchange factor (GEF) and transmit signals to their downstream effectors. Following signal t...

Keyword

AI 본문요약
AI-Helper 아이콘 AI-Helper

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문제 정의

  • 본고에서는 기존에 발표된 5개 subfamily에 속하는 Ras GTPase들의 역할과 기능을 알아보고 이를 조절하는 RasGAP 분자들에 최신의 연구결과들을 인체의 질병과의 관련성을 위주로 하여 요약하였다. 특히 인간 게놈 분석 결과 예측된 14종의 RasGAP 분자들이[12] RasGAP의 역할 이외에도 일부는 종양 억제자(tumor suppressor)로서의 생리학적 기능을 하고 있음을 제시한 연구결과들을 소개한다.
  • 본고에서는 기존에 발표된 5개 subfamily에 속하는 Ras GTPase들의 역할과 기능을 알아보고 이를 조절하는 RasGAP 분자들에 최신의 연구결과들을 인체의 질병과의 관련성을 위주로 하여 요약하였다. 특히 인간 게놈 분석 결과 예측된 14종의 RasGAP 분자들이[12] RasGAP의 역할 이외에도 일부는 종양 억제자(tumor suppressor)로서의 생리학적 기능을 하고 있음을 제시한 연구결과들을 소개한다.
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