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Sox4 단백질에 의한 β-catenin의 분해 유도 기전 KCI 등재

Sox4 Induces Degradation of β-catenin by Promoting Ubiquitination

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대한구강악안면병리학회지 (The Korean Journal of Oral and Maxillofacial Pathology)
대한구강악안면병리학회 (Korean Academy Of Oral And Maxillofacial Pathology)
초록

β-catenin is a cytoplasmic protein that participates in the assembly of cell-cell adherens junctions by binding cadherins to the cytoskeleton. In addition, it is a key component of the Wnt signaling pathway. Activation of this pathway triggers the accumulation of β-catenin in the nucleus, where it activates the transcription of target genes. Abnarmal accumulation of β -catenin is characteristic of polyposis coli(APC) or Axin tumor suppressor proteins, which regulates β-catenin degradation, or activating mutations in β-catenin molecule itself. Here we show that overexpression of Sox4 down-regulates wild type β-catenin in HEK 293 cells. The inhibitory effect of Sox4 on wild type β-catenin is apparently mediated by the ubiquitin- proteasoem system and requires an active glycogen synthase kinase 3β(GSK3β). Mutations in the N-terminus of β -catenin(S33Y) which compromise its degradation by the proteasomes or inhibition of GSK3β activity rendered β-catenin resistant to down-regulation by Sox4. In light of recent evidence that Sox4 expression is activated in colon and other tumors with β-catenin dysregulation, our findings suggest that Sox4 is part of a feedback inhibitory pathway for Wnt signaling in normal cells. Moreover, the mutations in APC, Axin or β-catenin in cancer cells appear to render β-catenin resistant to the effects of Sox4 inhibition.

목차
I. 서 론
 II. 재료 및 방법
  1. 세포배양과 transfection
  2. Total RNA 추출과 RT-PCR
  3. Plasmids
  4. Immunoprecipitation과 Immunoblotting
  5. Luciferase 리포터 유전자 분석
 III. 결과 및 고찰
  1. Sox4에 의한 정상 β-catenin의 저해
  2. Sox4에 의한 β-catenin/TCF 전사활성의 저해
  3. Sox4에 의한 β-catenin의 저해에서 GSK3β와 proteasome system의 역할
 IV. 참고문헌
저자
  • 김수아(조선대학교 치과대학 구강병리학교실) | Soo A Kim
  • 임경수(조선대학교 치과대학 구강병리학교실) | Kyung Soo Lim
  • 윤정훈(조선대학교 치과대학 구강병리학교실) | Jung Hoon Yoon correspondence
  • 안상건(조선대학교 치과대학 구강병리학교실) | Sang Gun Ahn correspondence