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


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. [BMB Reports 2021; 54(6): 305-310].

SUBMITTER: Park S 

PROVIDER: S-EPMC8249880 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Park Seulki S   Kim Kidae K   Haam Keeok K   Ban Hyun Seung HS   Kim Jung-Ae JA   Park Byoung Chul BC   Park Sung Goo SG   Kim Sunhong S   Kim Jeong-Hoon JH  

BMB reports 20210601 6


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 mitochon  ...[more]

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