title: Cereblon in health and disease.
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.
authors.affiliation: 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.|Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan, South Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Ko
authors.affiliation: 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.
authors.forename: Bayalagmaa
authors.initials: B
authors.lastname: Nyamaa
authors.affiliation: 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.|Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan, South Korea.
authors.forename: Sung Ryul
authors.initials: SR
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.affiliation: 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.
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.affiliation: School of Life Sciences and National Leading Research Laboratory for Ion Channels, Gwangju Institute Science and Technology, Gwangju, 500-712, South Korea.
authors.forename: Chul-Seung
authors.initials: CS
authors.lastname: Park
authors.affiliation: Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.affiliation: 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.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D044767:Ubiquitin-Protein Ligases; D055372:AMP-Activated Protein Kinases; D010447:Peptide Hydrolases
keywords: AMPK; BKCa; Cereblon; E3 ligase complex; Immunomodulatory drugs; Mental retardation