Publications by authors named "Kenta Kainoh"
Article Synopsis
- The study investigates two cases of extremely low HDL cholesterol levels linked to mutations in the ABCA1 gene, which is important for cholesterol transport, particularly in Tangier disease.
- In the first case, a 20-year-old woman with multiple health issues showed mutations leading to decreased cholesterol efflux and ABCA1 protein levels, while also having another condition called Krabbe disease.
- The second case involved a 51-year-old woman with similar low HDL levels and different mutations confirming Tangier disease, highlighting the complexity of mutations and their pathogenic mechanisms.
The endoplasmic reticulum (ER)-embedded transcription factors, sterol regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to the Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here, we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at the ER.
View Article and Find Full Text PDFMetabolism is one of the vital functions of cells and living organisms, and the systems to sense and respond to the metabolic alterations play pivotal roles in a plethora of biological processes, including cell proliferative activities, immune cell functions, aging processes, and neuronal functions. Recently, we have reported that a transcriptional cofactor, C-terminal binding protein 2 (CtBP2), serves as a critical metabolite sensor in this context. CtBP2 has a structural pocket called Rossmann fold to accommodate metabolites, and it has been reported to be activated upon binding to NADH/NAD.
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- In the early stages of obesity, insulin secretion increases as a protective measure to keep glucose levels stable, but this can’t last forever, leading to the failure of β cells and the onset of diabetes.
- The protein CtBP2 plays a vital role in regulating insulin gene expression in β cells by interacting with another factor, NEUROD1, which helps to open up chromatin at the insulin gene promoter.
- Reduced levels of CtBP2 in pancreatic islets are observed in both mouse models and humans with obesity, and mice lacking CtBP2 specifically in β cells show glucose intolerance and impaired insulin secretion, indicating its importance in maintaining β cell health and offering potential targets for obesity-related treatments.
Article Synopsis
- Maintaining the balance of metabolism is really important, but too much food can mess it up, especially in obesity.
- Researchers found out how two important proteins, PPARα and CtBP2, interact in a way that can slow down fat processing when there's extra fat in the body.
- In obese people, this interaction gets stronger, making it harder for the body to break down fat, which could lead to new treatments for obesity-related diseases.
Biological systems to sense and respond to metabolic perturbations are critical for the maintenance of cellular homeostasis. Here we describe a hepatic system in this context orchestrated by the transcriptional corepressor C-terminal binding protein 2 (CtBP2) that harbors metabolite-sensing capabilities. The repressor activity of CtBP2 is reciprocally regulated by NADH and acyl-CoAs.
View Article and Find Full Text PDFCtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF2.
Biochem Biophys Res Commun
July 2021
Article Synopsis
- Molecular oxygen is crucial for aerobic organisms but can cause oxidative damage, leading to various diseases due to insufficient antioxidative defense.
- Cells have evolved systems regulated by transcription factors NRF1 and NRF2 to manage oxidative stress, but the complexities and redundancies in these systems are not fully understood.
- This study identifies C-terminal binding protein 2 (CtBP2) as a key partner for NRFs, necessary for forming complexes that enhance the expression of antioxidant genes in response to oxidative stress, highlighting potential therapeutic targets for enhancing antioxidative defense.
The epithelial to mesenchymal transition (EMT) is a cell intrinsic program controlling cellular morphological and phenotypic remodeling in a wide range of biological processes. Despite the accumulating evidence, the transcriptional networks regulating EMT still remain to be elucidated. In this study, we demonstrate that C-terminal binding protein 2 (CtBP2), a critical transcriptional co-repressor harboring pyridine nucleotide sensing capability, orchestrates the EMT program at least in part through a novel transcriptional interaction with an octamer transcription factor, OCT1 (POU2F1, POU class 2 homeobox 1).
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