A5015763735- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Immune cells in cancer
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Neurological Disease Mechanisms and Treatments
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Peptidase Inhibition and Analysis
- Cardiac electrophysiology and arrhythmias
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Immune Response and Inflammation
- RNA Research and Splicing
- Cell death mechanisms and regulation
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Calcium signaling and nucleotide metabolism
- 14-3-3 protein interactions
- Barrier Structure and Function Studies
- Cancer-related Molecular Pathways
- Neurogenesis and neuroplasticity mechanisms
- Genomics, phytochemicals, and oxidative stress
University of Tsukuba
2015-2025
ENVIRON (United States)
2016
Stanford University
2006-2015
The University of Tokyo
2002-2005
Bax, a proapoptotic member of the Bcl-2 family, localizes largely in cytoplasm but redistributes to mitochondria response apoptotic stimuli, where it induces cytochrome<i>c</i> release. In this study, we show that phosphatidylinositol 3-OH kinase (PI3K)-Akt pathway plays an important role regulation Bax subcellular localization. We found LY294002, PI3K inhibitor, blocked effects serum prevent translocation and expression active form suppressed staurosporine-induced translocation, suggesting...
Life and death decisions are made by integrating a variety of apoptotic survival signals in mammalian cells. Therefore, there is likely to be common mechanism that integrates multiple adjudicating between the alternatives. In this study, we propose 14-3-3 represents such an integration point. Several proapoptotic proteins commonly become associated with upon phosphorylation survival-mediating kinases as Akt. We reported previously cellular stresses induce c-Jun NH2-terminal kinase...
Brain aging causes a wide variety of changes at the molecular and cellular levels, leading to decline cognitive functions increased vulnerability neurodegenerative disorders. The research aimed understanding brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, spatial transcriptomic analyses have facilitated on dynamic occurring within neurons, glia, other cells along with their impacts intercellular...
The brain, the most important component of central nervous system (CNS), is protected by multiple intricate barriers that strictly regulate entry abnormal proteins and cells. Thus, brain often described as an organ with immune privilege. Within parenchyma, microglia are thought to be primary resident cells, no other immune-related cells present under normal conditions. On hand, recent studies in meningeal border regions have revealed presence meningeal-specific lymphatic vessels channels...
Micronuclei (MN) serve as well-established markers of genomic instability. MN arise from various stresses, such segregation errors and mechanical stress, are subsequently eliminated by the autophagy pathway. It has been suggested that traditionally considered cancer cells, often without recognized functional significance. Meanwhile, we recently discovered act mediators in regulating microglial characteristics. Neurons produce response to migrating stress during developmental stage release...
The brain, the most important component of central nervous system (CNS), is protected by multiple intricate barriers that strictly regulate entry proteins and cells. Thus, brain often described as an organ with immune privilege. Within parenchyma, microglia are thought to be primary resident cells, no other immune-related cells present under normal conditions. On hand, recent studies in meningeal border regions have revealed presence meningeal-specific lymphatic vessels channels connect...
Voltage-gated Ca2+ channels (VGCCs) play a key role in neuronal signaling but can also contribute to cellular dysfunction and death under pathological conditions such as stroke neurodegenerative diseases. We report that activation of N-methyl-d-aspartic acid receptors causes internalization degradation CaV1.2 channels, resulting decreased entry reduced toxicity. requires binding phosphatidylinositol 3-phosphate 5-kinase (PIKfyve), lipid kinase which generates (3,5)-bisphosphate...
Substrate-specific protein degradation mediated by the ubiquitin proteasome system (UPS) is crucial for proper function of cell. Proteins are specifically recognized and ubiquitinated ligases (E3s) then degraded proteasome. BTB proteins act as substrate recognition subunit that recruits their cognate substrates to Cullin 3-based multisubunit E3s. Recently, it was reported missense mutations in KLHL7, a BTB-Kelch protein, related autosomal dominant retinitis pigmentosa (adRP). However,...
Proteasomes are highly sophisticated protease complexes that degrade non-lysosomal proteins, and their proper regulation ensures various biological functions such as spermatogenesis. The proteasome-associated PA200 ECPAS, predicted to function during spermatogenesis; however, male mice lacking each of these genes sustain fertility, raising the possibility proteins complement other. To address this issue, we explored possible roles spermatogenesis by producing (double-knockout mice; dKO...
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4-20Q; SCA6: 20-33Q) in the carboxyl(C)-terminal cytoplasmic domain of alpha(1A) voltage-dependent calcium channel (Ca(v)2.1). Although 75-85-kDa Ca(v)2.1 C-terminal fragment (CTF) toxic cultured cells, its existence human brains and role SCA6 pathogenesis remains unknown. Here, we investigated whether polyQ alters expression pattern...
Application of high concentrations sodium ascorbate suppresses necrosis caused by the expression recombinant proteins in Nicotiana benthamiana, resulting an increase protein accumulation.
Abstract Hevin is a secreted extracellular matrix protein that encoded by the SPARCL1 gene. Recent studies have shown plays an important role in regulating synaptogenesis and synaptic plasticity. Mutations gene increase risk of autism spectrum disorder (ASD). However, molecular basis how mutations ASD not been fully understood. In this study, we show one associated with impairs normal secretion. We identified mutants lacking EF-hand motif through analyzing ASD-related mice vulnerable...
Many cellular stresses cause damages of intracellular proteins, which are eventually degraded by the ubiquitin and proteasome system. The is a multicatalytic protease complex composed 20S core particle activators that regulate activity. Extracellular mutants 29 (Ecm29) 200 kDa protein encoded KIAA0368 gene, associates with proteasome, but its role largely unknown. Here, we generated KIAA0368-deficient mice investigated function Ecm29 in stress response. showed normal peptidase activity...
Nuclear factor-kappaB (NF-κB) is critical for the expression of multiple genes involved in inflammatory responses and cellular survival. NF-κB normally sequestered cytoplasm through interaction with an inhibitor (IκB), but stimulation induces proteasomal degradation IκB, followed by nuclear translocation. The IκB mediated a SCF (Skp1-Cullin1-F-box protein)-type ubiquitin ligase complex that post-translationaly modified ubiquitin-like molecule Nedd8. In this study, we report BRCA1-associated...
ABSTRACTPrecise regulation of RNA metabolism is crucial for dynamic gene expression and controlling cellular functions. In the nervous system, defects in are implicated disturbance brain homeostasis development. Here, we report that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), deubiquitinates terminal uridylyl transferase 1 (TUT1) changes global metabolism. We found USP15 redistributes TUT1 from nucleolus to nucleoplasm, resulting stabilization U6 snRNA. also lack Usp15...
Abstract Microglia are resident macrophages that critical for brain development and homeostasis. Microglial morphology is dynamically changed during postnatal stages, leading to regulating synaptogenesis synapse pruning. Moreover, it has been well known the shape of microglia also altered in response detritus apoptotic cells pathogens such as bacteria viruses. Although morphologic changes crucial acquiring microglial functions, exact mechanism which controls their not fully understood. Here,...