Cereblon in health and disease

Hyoung Kyu Kim; Tae Hee Ko; Bayalagmaa Nyamaa; Sung Ryul Lee; Nari Kim; Kyung Soo Ko; Byoung Doo Rhee; Chul-Seung Park; Bernd Nilius; Jin Han

doi:10.1007/s00424-016-1854-1

Cereblon in health and disease

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

Authors

Hyoung Kyu Kim^{1

2}, Tae Hee Ko¹, Bayalagmaa Nyamaa¹, Sung Ryul Lee^{1

2}, Nari Kim¹, Kyung Soo Ko¹, Byoung Doo Rhee¹, Chul-Seung Park³, Bernd Nilius⁴, Jin Han⁵

Affiliations

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.

PMID: 27343012
DOI: 10.1007/s00424-016-1854-1

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.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism
Animals
Carrier Proteins / metabolism
Humans
Peptide Hydrolases / metabolism*
Protein Binding / physiology
Signal Transduction / physiology
Ubiquitin-Protein Ligases / metabolism*

Substances

Carrier Proteins
Ubiquitin-Protein Ligases
AMP-Activated Protein Kinases
Peptide Hydrolases