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Related Experiment Video

Updated: Oct 3, 2025

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

Cereblon contributes to cardiac dysfunction by degrading Cav1.2α.

Nammi Park¹, Jubert Marquez¹, Trong Kha Pham¹

¹Basic Research Laboratory, Department of Physiology, College of Medicine, Smart Marine Therapeutic Center, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Republic of Korea.

European Heart Journal

|February 22, 2022

Summary

Cereblon (CRBN) degrades Cav1.2α, worsening heart failure. Reducing CRBN levels or using CRBN degraders enhances cardiac function and may treat heart failure with reduced ejection fraction (HFrEF).

Keywords:

Cav1.2α Cereblon Heart failure PROTAC Ubiquitination

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Last Updated: Oct 3, 2025

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

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Published on: September 18, 2017

Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry

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Published on: September 28, 2016

Primary Culture of Adult Rat Heart Myocytes

Primary Culture of Adult Rat Heart Myocytes

Published on: June 16, 2009

Area of Science:

Cardiovascular Biology
Molecular Cardiology
E3 Ubiquitin Ligase Biology

Background:

Cereblon (CRBN) targets proteins for degradation via the E3 ubiquitin ligase complex.
L-type voltage-dependent Ca2+ channel (LTCC) dysfunction is key in heart failure with reduced ejection fraction (HFrEF).
The role of CRBN in regulating LTCC Cav1.2α during cardiac dysfunction is not well understood.

Purpose of the Study:

To investigate the role of CRBN in HFrEF.
To explore CRBN's direct regulatory role in Cav1.2α activity.
To assess CRBN as a therapeutic target for myocardial dysfunction.

Main Methods:

Analysis of cardiac tissues from HFrEF patients and controls.
In vivo and ex vivo studies using CRBN knockout mouse models.
Investigation of CRBN-Cav1.2α interaction using genetic and pharmacological approaches, including a PROTAC degrader (TD-165).

Main Results:

Increased CRBN levels were observed in HFrEF cardiac tissues.
CRBN knockout mice showed enhanced cardiac contractility and LTCC current (ICaL).
CRBN directly interacts with Cav1.2α, promoting its ubiquitination and degradation, thereby reducing ICaL. Depletion of CRBN increased ICaL and protected against cardiomyopathy.

Conclusions:

Cereblon selectively degrades Cav1.2α, contributing to cardiac dysfunction in HFrEF.
Reducing CRBN levels or targeting CRBN degradation presents a promising therapeutic strategy for HFrEF.