대한의생명과학회지 (Biomedical Science Letters)

  • 제24권2호
  • /
  • Pages.64-75
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  • 2018
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  • 1738-3226(pISSN)
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  • 2288-7415(eISSN)
대한의생명과학회 (The Korean Society for Biomedical Laboratory Sciences)
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A Missense Variant (R239Q) in CCN3 Induces Aberrant Apoptosis in the Developing Mouse Brain

  • Kim, Hyunduk (Department of Biochemistry, Chungbuk National University) ;
  • Yang, Hayoung (Department of Biochemistry, Chungbuk National University) ;
  • Woo, Dong Kyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Jang, Sung-Wuk (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Shim, Sungbo (Department of Biochemistry, Chungbuk National University)
  • 투고 : 2018.05.29
  • 심사 : 2018.06.04
  • 발행 : 2018.06.30
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초록

CCN3 (also known as NOV, Nephroblastoma overexpressed) proteins are involved in various pathologies during different developmental stages. We have previously shown that intracellular levels and normal extracellular secretion of CCN3 are important for neuronal differentiation. Furthermore, we demonstrated that a single amino acid in the CCN3 TSP-1 domain is important for extracellular secretion and that palmitoylation of CCN3 is required in this process. However, the effect of abnormal CCN3 accumulation on cells remains to be studied. Here, we found mutations in the TSP-1 domain of CCN3 that led to intracellular accumulation and abnormal aggregation of CCN3. It was observed that this mutation resulted in a phenomenon similar to neurodegeneration when overexpressed in the developing mouse cortex. This mutation also confirmed the activation of apoptotic gene expression in Neuro2a cells. In addition, we confirmed the in vivo transcriptional changes induced by this mutation using microarray analysis. We observed a significant increase in the expression of Anp32a, an apoptosis-related gene. Collectively, these results indicate that a single mutation in CCN3 can lead to abnormal cell death if it shows intracellular accumulation and abnormal aggregation.

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참고문헌

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