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Mining of Caspase-7 Substrates Using a Degradomic Approach  

Jang, Mi (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Park, Byoung Chul (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Kang, Sunghyun (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Do Hee (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Cho, Sayeon (College of Pharmacy, Chung-Ang University)
Lee, Sang-Chul (Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
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)
Publication Information
Molecules and Cells / v.26, no.2, 2008 , pp. 152-157 More about this Journal
Abstract
Caspases play critical roles in the execution of apoptosis. Caspase-3 and caspase-7 are closely related in sequence as well as in substrate specificity. The two caspases have overlapping substrate specificities with special preference for the DEVD motif. However, they are targeted to different subcellular locations during apoptosis, implying the existence of substrates specific for one or other caspase. To identify new caspase-7 substrates, we digested cell lysates obtained from the caspase-3-deficient MCF-7 cell line with purified recombinant caspase-7, and analyzed spots that disappeared or decreased by 2-DE (we refer to this as the caspase-7 degradome). Several proteins with various cellular functions underwent caspase-7-dependent proteolysis. The substrates of capase-7 identified by the degradomic approach were rather different from those of caspase-3 (Proteomics, 4, 3429-3435, 2004). Among the candidate substrates, we confirmed that Valosin-containing protein (VCP) was cleaved by both capspase-7 and caspase-3 in vitro and during apoptosis. Cleavage occurred at both $DELD^{307}$ and $DELD^{580}$. The degradomic study yielded several candidate caspase-7 substrates and their further analysis should provide valuables clues to the functions of caspase-7 during apoptosis.
Keywords
2-DE; apoptosis; caspase-7; degradome; VCP;
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Times Cited By KSCI : 3  (Citation Analysis)
Times Cited By Web Of Science : 10  (Related Records In Web of Science)
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