Related Experiment Video

Updated: Nov 22, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.5K

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

Seulki Park1, Kidae Kim2, Keeok Haam3

  • 1Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141; Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea.

BMB Reports
|January 7, 2021
PubMed

Insights

Cereblon (CRBN) protein is vital for maintaining mitochondrial health. Its depletion causes oxidative stress and cell death, highlighting CRBN

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Biochemistry

Background:

  • Cereblon (CRBN) is a known multi-functional protein involved in E3 ligase complexes and acting as a molecular chaperone.
  • The precise functions of CRBN within mitochondria remain largely uncharacterized.

Purpose of the Study:

  • To investigate the specific roles of Cereblon (CRBN) in mitochondrial function and cellular homeostasis.
  • To determine the consequences of CRBN depletion on mitochondrial integrity and cell viability.

Main Methods:

  • Knockdown of CRBN expression using RNA interference.
  • Assessment of mitochondrial oxidative stress and calcium levels.
  • Measurement of mitochondrial membrane potential.
  • Long-term CRBN depletion utilizing PROteolysis TArgeting Chimera (PROTAC) technology.

Main Results:

  • CRBN knockdown induced significant mitochondrial oxidative stress and calcium overload.
  • Disruption of mitochondrial membrane potential was observed upon CRBN depletion.
  • Prolonged CRBN absence via PROTAC led to irreversible mitochondrial dysfunction and subsequent cell death.

Conclusions:

  • Cereblon (CRBN) plays a critical role in maintaining mitochondrial homeostasis.
  • CRBN is essential for preventing mitochondrial dysfunction and ensuring cell survival.

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