Cereblon regulates the production of hepatic fibroblast growth factor 23 in diabetes.

Cereblon (CRBN) is an extensively expressed protein involved in crucial physiological processes. This study reveals CRBN's role in governing hepatic fibroblast growth factor 23 (FGF23) expression and production via the cyclic adenosine monophosphate (cAMP) pathway in diabetic conditions. The expressions of hepatic Crbn, Yin Yang 1 (Yy1), and Fgf23 genes were significantly increased in diabetic mice and forskolin (FSK)-treated primary hepatocytes, correlating with elevated FGF23 production.

Enhanced homeostatic sleep response and decreased neurodegenerative proteins in cereblon knock-out mice.

Energy homeostasis and sleep have a bidirectional relationship. Cereblon (CRBN) regulates energy levels by ubiquitinating the AMP-activated protein kinase(AMPK), an energy sensor. However, whether CRBN participates in sleep is unclear.

Enhancement of the SESN2-SHP cascade by melatonin ameliorates hepatic gluconeogenesis by inhibiting the CRBN-BTG2-CREBH signaling pathway.

Melatonin is involved in the regulation of various biological functions. Here, we explored a novel molecular mechanism by which the melatonin-induced sestrin2 (SESN2)-small heterodimer partner (SHP) signaling pathway protects against fasting- and diabetes-mediated hepatic glucose metabolism. Various key gene expression analyses were performed and multiple metabolic changes were assessed in liver specimens and primary hepatocytes of mice and human participants.

Induction of SIRT1 by melatonin improves alcohol-mediated oxidative liver injury by disrupting the CRBN-YY1-CYP2E1 signaling pathway.

Alcoholic liver disease is the most prevalent chronic liver disease. Melatonin is known to control many vital processes. Here, we explored a novel molecular mechanism by which melatonin-induced SIRT1 signaling protects against alcohol-mediated oxidative stress and liver injury.

BK channel blocker paxilline attenuates thalidomide-caused synaptic and cognitive dysfunctions in mice.

Thalidomide is a widely prescribed immunomodulatory drug (iMiD) for multiple myeloma, but causes reversible memory loss in humans. However, how thalidomide causes cognitive dysfunction at a cellular and molecular level has not been demonstrated. We studied the effect of thalidomide on synaptic functions and cognitive behaviors using a mouse model.

Cereblon Maintains Synaptic and Cognitive Function by Regulating BK Channel.

Mutations in the () gene cause human intellectual disability, one of the most common cognitive disorders. However, the molecular mechanisms of -related intellectual disability remain poorly understood. We investigated the role of in synaptic function and animal behavior using male mouse and models.

Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.

Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome.

Inhibition of cereblon by fenofibrate ameliorates alcoholic liver disease by enhancing AMPK.

Alcohol consumption exacerbates alcoholic liver disease by attenuating the activity of AMP-activated protein kinase (AMPK). AMPK is activated by fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, and inhibited by direct interaction with cereblon (CRBN), a component of an E3 ubiquitin ligase complex. Based on these preliminary findings, we investigated that CRBN would be up-regulated in the liver by alcohol consumption and that CRBN deficiency would ameliorate hepatic steatosis and pro-inflammatory responses in alcohol-fed mice by increasing AMPK activity.

Depletion of the cereblon gene activates the unfolded protein response and protects cells from ER stress-induced cell death.

Previous studies showed that cereblon (CRBN) binds to various cellular target proteins, implying that CRBN regulates a wide range of cell responses. In this study, we found that deletion of the Crbn gene desensitized mouse embryonic fibroblast cells to various cell death-promoting stimuli, including endoplasmic reticulum stress inducers. Mechanistically, deletion of Crbn activates pathways involved in the unfolded protein response prior to ER stress induction.

Functional effects of a pathogenic mutation in Cereblon (CRBN) on the regulation of protein synthesis via the AMPK-mTOR cascade.

Initially identified as a protein implicated in human mental deficit, cereblon (CRBN) was recently recognized as a negative regulator of adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. Here, we present results showing that CRBN can effectively regulate new protein synthesis through the mammalian target of rapamycin (mTOR) signaling pathway, a downstream target of AMPK. Whereas deficiency of Crbn repressed protein translation via activation of the AMPK-mTOR cascade in Crbn-knock-out mice, ectopic expression of the wild-type CRBN increased protein synthesis by inhibiting endogenous AMPK.

Cereblon inhibits proteasome activity by binding to the 20S core proteasome subunit beta type 4.

In humans, mutations in the gene encoding cereblon (CRBN) are associated with mental retardation. Although CRBN has been investigated in several cellular contexts, its function remains unclear. Here, we demonstrate that CRBN plays a role in regulating the ubiquitin-proteasome system (UPS).

Mass production of polyfluorene nanowires using a melt-assisted wetting method.

Herein is a description of the mass production of poly(9, 9-dioctylfluorene-co-benthiadiazole) (F8BT) and poly(9, 9-dioctylfluorene) (PFO) nanowires (NWs) using a melt-assisted wetting method with an anodic alumina membrane. The conjugated polymer NWs had a uniform shape (D = 250-300 nm/L = 10-30 microm) and a defect-free smooth surface. Optical properties were investigated by UV-vis, photoluminescent spectroscope, and fluorescent optical microscope.

Functional modulation of AMP-activated protein kinase by cereblon.

Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation.

Induction of cereblon by NF-E2-related factor 2 in neuroblastoma cells exposed to hypoxia-reoxygenation.

Cereblon is a protein encoded by the CRBN gene, which has been associated with human autosomal recessive nonsyndromic mental retardation. However, little is known about the regulation of CRBN expression. Following exposure of mouse neuroblastoma N2A cells to hypoxia/reoxygenation (H/R), mRNA and protein expression of CRBN were increased.

Statistical analysis of metal-molecule contacts in alkyl molecular junctions: sulfur versus selenium end-group.

We fabricated a large number of microscale via-hole structure molecular devices (2240 devices) using octane-Se [CH3(CH2)7Se] self assembled monolayers (SAMs) and compared their charge transport properties with those of octane-S [CH3(CH2)7S] SAMs molecular devices in terms of current density, resistance, and tunneling decay coefficient. The device yield of the "working" octane-Se molecular devices was found to be approximately 1.7% (38/2240), which was similar to the yield of approximately 1.

Synthesis of L-phenylalanine stabilized gold nanoparticles and their thermal stability.

Here we described the two synthesis methods of L-phenylalanine (L-phe) coated gold nanoparticles through a reduction of aqueous chloroaurate ions directly by L-phe, and also the borohydride reduction of chloroauric acid followed by capping with L-phe molecules. Phenylalanine reduced gold nanoparticles and the phenylalanine capped gold nanoparticles were evaluated by transmission electron microscope and UV-vis spectroscopy, and then their thermal stabilities were compared. We found that the phenylalanine reduced gold nanoparticles were unstable and form linearly arranged aggregates on aging, while as the phenylalanine capped gold nanoparticles were stable for months in ambient condition.

Insertion of a specular reflective and transmissive nano-oxide layer into giant magnetoresistance spin-valve structure.

We have studied the influence of the insertion of a nano-oxide layer (NOL) into a magnetic GMR spin-valve. It was found that the spin-valve with NOL has a higher GMR ratio than that of the normal spin-valve without NOL. Naturally formed NOL without vacuum break shows a uniform layer, which effectively suppresses the current shunt, resulting in the reduction of the sheet resistance of GMR.

Effect of aluminum on the formation of silver metal quantum dots in sol-gel derived alumino-silicate glass film.

The effect of aluminum incorporation on silver metal quantum dots formation in the alumino-silicate glass film processed by sol-gel process was investigated. The sol-gel derived glass was coated onto the silica glass plate by spin coating with the mixture solution of tetraethyl orthosilicate (TEOS), C2H5OH, H2O, AgNO3, Al(NO3)3. 39H2O, and HNO3 with the molar ratios of Ag/Si = 0.

Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain.

Large-conductance Ca2+-activated K+ (BK(Ca)) channels are activated by membrane depolarization and modulated by intracellular Ca2+. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy-terminus of the BK(Ca) channel alpha subunit (Slo). Rat CRBN contained the N-terminal domain of the Lon protease, a 'regulators of G protein-signaling' (RGS)-like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites.