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Pflugers Arch. 2016 Aug;468(8):1299-309. doi: 10.1007/s00424-016-1854-1. Epub 2016 Jun 24.

Cereblon in health and disease.

Author information

1
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Bokji-ro 75, Busanjin-gu, Busan, 47392, South Korea.
2
Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan, South Korea.
3
School of Life Sciences and National Leading Research Laboratory for Ion Channels, Gwangju Institute Science and Technology, Gwangju, 500-712, South Korea.
4
Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
5
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Bokji-ro 75, Busanjin-gu, Busan, 47392, South Korea. phyhanj@inje.ac.kr.

Abstract

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that has been linked to autosomal recessive non-syndromic mental retardation. Several key findings suggest diverse roles of CRBN, including its regulation of the large-conductance calcium- and voltage-activated potassium (BKCa) channels, regulation of thalidomide-binding proteins, and mediation of lenalidomide treatment in multiple myeloma. Recent studies also indicate that CRBN is involved in energy metabolism and negatively regulates AMP-activated protein kinase signaling. Mice with genetic depletion of CRBN are resistant to various stress conditions including a high-fat diet, endoplasmic reticulum stress, ischemia/reperfusion injury, and alcohol-related liver damage. In this review, we discuss the various roles of CRBN in human health and disease and suggest avenues for further research to enhance our basic knowledge and clinical application of CRBN.

KEYWORDS:

AMPK; BKCa; Cereblon; E3 ligase complex; Immunomodulatory drugs; Mental retardation

PMID:
27343012
DOI:
10.1007/s00424-016-1854-1
[Indexed for MEDLINE]

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