Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Coiled-Coil Domain-Containing Protein 98 (CCDC98) Regulates Cyclin B1 Expression by Affecting WTAP Protein Stability

WTAP 단백질의 안정성을 통한 CCDC98 단백질의 cyclin B1 발현 조절

  • Oh, Yun-Jung (Department of Biological Sciences, Sungkyunkwan University) ;
  • Lee, Eun-Hee (Department of Biological Sciences, Sungkyunkwan University) ;
  • Lee, Il-Kyu (Department of Family Medicine, The Catholic University of Korea) ;
  • Kim, Kyung-Soo (Department of Family Medicine, The Catholic University of Korea) ;
  • Kim, Hong-Tae (Department of Biological Sciences, Sungkyunkwan University)
  • 오윤정 (성균관대학교 생명과학과) ;
  • 이은희 (성균관대학교 생명과학과) ;
  • 이일규 (가톨릭대학교 가정의학과) ;
  • 김경수 (가톨릭대학교 가정의학과) ;
  • 김홍태 (성균관대학교 생명과학과)
  • Received : 2011.05.09
  • Accepted : 2011.07.08
  • Published : 2011.08.30
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Abstract

Coiled-coil domain-containing protein 98 (CCDC98) plays a role in G2/M DNA damage checkpoint pathways by recruiting breast cancer 1 (BRCA1)-A complex to the DNA-damaged sites. However, the molecular mechanism of CCDC98 on the DNA damage-induced G2/M checkpoint pathways is unclear. In this study, we identifed Wilms tumor 1-associating protein (WTAP) as a novel CCDC98-binding protein, using tandem affinity purification. We confirmed the association between CCDC98 and WTAP using in vivo and in vitro binding assays. We demonstrated that CCDC98 regulates cyclin B1 expression by affecting WTAP protein stability. Based on these results, we suggest that CCDC98 may act as a novel cell cycle regulator by regulating the expression level of cyclin B1.

CCDC98 단백질은 BRCA1-A 복합체를 DNA 손상 부위로 이동시킴으로써 DNA손상에 의하여 유도되는 G2/M cell cycle checkpoint에 중요한 역할을 한다고 알려져 있다. 하지만 많은 연구에도 불구하고 CCDC98 단백질의 기능에 대해서 알려진 바가 거의 없다. 본 연구는 CCDC98 단백질의 기능을 밝히고자 tandem affinity purification 방법을 수행하였다. 그 결과 Wilms tumor 1-associating protein (WTAP)을 CCDC98의 결합 단백질로 분리 동정하였다. 이들 단백질의 결합을 in vivo and in vitro binding assays를 통하여 확인하였다. 또한, CCDC98 단백질이 cyclin B1의 발현을 억제함을 확인하였는데, 이는 WTAP 단백질의 발현을 조절함으로써 이루어진다는 것을 확인하였다. 이는 CCDC98 단백질이 새로운 세포주기 조절자라는 것을 증명하는 결과이다.

Keywords

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