Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Protein Disulfide Isomerase Is Cleaved by Caspase-3 and -7 during Apoptosis

  • Na, Kyung Sook (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Byoung Chul (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jang, Mi (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Sayeon (Department of Pharmacy, Chung-Ang University) ;
  • Lee, Do Hee (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Sunghyun (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Chong-Kil (Department of Pharmacy, Chungbuk National University) ;
  • Bae, Kwang-Hee (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Sung Goo (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2007.04.12
  • Accepted : 2007.05.23
  • Published : 2007.10.31
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Abstract

Apoptotic signals are typically accompanied by activation of aspartate-specific cysteine proteases called caspases, and caspase-3 and -7 play crucial roles in the execution of apoptosis. Previously, using the proteomic approach, protein disulfide isomerase (PDI) was found to be a candidate substrate of caspase-7. This abundant 55 kDa protein introduces disulfide bonds into proteins (via its oxidase activity) and catalyzes the rearrangement of incorrect disulfide bonds (via its isomerase activity). PDI is abundant in the ER but is also found in non-ER locations. In this study we demonstrated that PDI is cleaved by caspase-3 and -7 in vitro. In addition, in vivo experiment showed that it is cleaved during etoposide-induced apoptosis in HL-60 cells. Subcellular fractionation showed that PDI was also present in the cytosol. Furthermore, only cytosolic PDI was clearly digested by caspase-3 and -7. It was also confirmed by confocal image analysis that PDI and caspase-7 partially co-localize in both resting and apoptotic MCF-7 cells. Overexpression of cytosolic PDI (ER retention sequence deleted) inhibited cell death after an apoptotic stimulus. These data indicate that cytosolic PDI is a substrate of caspase-3 and -7, and that it has an anti-apoptotic action.

Keywords

Acknowledgement

Supported by : Korea Science & Engineering Foundation, Ministry of Health & Welfare

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