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http://dx.doi.org/10.5483/BMBRep.2021.54.6.218

Long-term depletion of cereblon induces mitochondrial dysfunction in cancer cells  

Park, Seulki (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Kidae (Division of Biomedical Informatics, Center for Genome Science, National Institute of Health, KCDC)
Haam, Keeok (Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Ban, Hyun Seung (Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Kim, Jung-Ae (Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology)
Park, Byoung Chul (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Park, Sung Goo (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Sunhong (Drug Discovery Center, LG Chem)
Kim, Jeong-Hoon (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Publication Information
BMB Reports / v.54, no.6, 2021 , pp. 305-310 More about this Journal
Abstract
Cereblon (CRBN) is a multi-functional protein that acts as a substrate receptor of the E3 ligase complex and a molecular chaperone. While CRBN is proposed to function in mitochondria, its specific roles are yet to be established. Here, we showed that knockdown of CRBN triggers oxidative stress and calcium overload in mitochondria, leading to disruption of mitochondrial membrane potential. Notably, long-term CRBN depletion using PROteolysis TArgeting Chimera (PROTAC) induced irreversible mitochondrial dysfunction, resulting in cell death. Our collective findings indicate that CRBN is required for mitochondrial homeostasis in cells.
Keywords
Calcium overload; Cell death; CRBN; Mitochondrial dysfunction; ROS;
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Times Cited By KSCI : 1  (Citation Analysis)
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