A5019310537- Reproductive Biology and Fertility
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
- Telomeres, Telomerase, and Senescence
- Autophagy in Disease and Therapy
- Genetics, Bioinformatics, and Biomedical Research
- Nerve injury and regeneration
- NF-κB Signaling Pathways
- Ion channel regulation and function
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Studies on Chitinases and Chitosanases
- 14-3-3 protein interactions
- Cytokine Signaling Pathways and Interactions
- Signaling Pathways in Disease
- interferon and immune responses
- Protease and Inhibitor Mechanisms
RIKEN Center for Biosystems Dynamics Research
2019-2020
RIKEN Center for Integrative Medical Sciences
2019
RIKEN
2000-2017
Systems Biology Institute
2014-2017
National Institute of Genetics
2005
National Institute for Basic Biology
2005
The Graduate University for Advanced Studies, SOKENDAI
2005
Molecular Oncology (United States)
2001
RIKEN BioResource Research Center
2000
Mutant alpha(1)-antitrypsin Z (alpha(1)-ATZ) protein, which has a tendency to form aggregated polymers as it accumulates within the endoplasmic reticulum of liver cells, is associated with development chronic injury and hepatocellular carcinoma in hereditary (alpha(1)-AT) deficiency. Previous studies have suggested that efficient intracellular degradation alpha(1)-ATZ correlated protection from disease alpha(1)-AT deficiency ubiquitin-proteasome system accounts for major route, but not sole...
The low affinity neurotrophin receptor p75NTR can mediate cell survival as well death of neural cells by NGF and other neurotrophins. To elucidate p75NTR-mediated signal transduction, we screened p75NTR-associated proteins a yeast two-hybrid system. We identified one positive clone named NADE (p75NTR-associated deathexecutor). Mouse has marked homology to the human HGR74 protein. specifically binds cell-death domain p75NTR. Co-expression induced caspase-2 caspase-3 activities fragmentation...
Abstract The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT phosphorylated at threonine 249 during mitosis by serine/threonine kinase CDK1. Clinicopathological analyses reveal phosphorylation occurs more frequently aggressive cancers. Using CRISPR/Cas9 genome editing, introduce substitution mutations endogenous locus find necessary for hTERT-mediated RNA dependent polymerase (RdRP)...
Mammalian metaphase II (mII) exit and embryogenesis are induced at fertilisation by a signal thought to come from the sperm protein, phospholipase C-zeta (PLCZ1). Meiotic progression can also be triggered without sperm, as in parthenogenesis, although classic mouse vivo parthenogenetic model, LT/Sv, fails meiosis I owing an unknown molecular etiology. Here, we dissect PLCZ1 specificity function address its ability interfere with maternal meiotic exit. Wild-type Plcz1 expression was...
Nerve growth factor (NGF) can induce apoptosis in neural cells via activation of the low affinity neurotrophin receptor p75NTR. NADE (p75NTR-associated celldeath executor) is a p75NTR-associated protein that mediates response to NGF by interacting with death domain p75NTR 293T, PC12, and nnr5 (Mukai, J., Hachiya, T., Shoji-Hoshino, S., Kimura, M. Nadano, D., Suvanto, P., Hanaoka, Li, Y., Irie, Greene, L. A., Sato, T. A. (2000) <i>J. Biol. Chem.</i> 275, 17566–17570). We performed extensive...
The low affinity neurotrophin receptor (p75NTR) has been shown to mediate the apoptosis signaling neural cells. However, specific mechanisms of intracellular signal transduction this process are largely unknown. To understand p75NTR-mediated transduction, we previously identified a protein that interacts with domain p75NTR, and named it p75NTR-associated cell deathexecutor (NADE). elucidate further utilized by p75NTR NADE, screened for NADE-binding protein(s) yeast two-hybrid method, 14-3-3ε...
Anaphase-promoting complex or cyclosome (APC/C) is a multisubunit ubiquitin ligase E3 that targets cell-cycle regulators. Cdc20 required for full activation of APC/C in M phase, and mediates substrate recognition. In vertebrates, Emi2/Erp1/FBXO43 inhibits APC/C-Cdc20, functions as cytostatic factor causes long-term phase arrest mature oocytes. this study, we found fragment corresponding to the zinc-binding region (ZBR) domain Emi2 progression, impairs association with core HEK293T cells....
The manipulation of mammalian metaphase II (mII) oocytes has illuminated the mechanisms fertilization and early embryogenesis is central to nuclear transfer. Although RNA interference (RNAi) would greatly facilitate this type manipulation, its application mature, developmentally competent mII not been evaluated. We report efficient RNAi by injection short interfering RNAs (siRNAs) into oocytes. levels target mRNA corresponding protein were rapidly efficiently reduced. siRNAs effective when...
Voltage-gated sodium channels (VGSCs) are transmembrane proteins required for the generation of action potentials in excitable cells and essential propagating electrical impulses along nerve cells. VGSCs complexes a pore-forming α subunit auxiliary β subunits, designated as β1/β1B-β4 (encoded by SCN1B-4B, respectively), which also function cell-cell adhesion. We previously reported structural basis trans homophilic interaction β4 subunit, contributes to its adhesive function. Here, using...
Abstract The β1, β2 and β4 subunits of voltage-gated sodium channels reportedly function as cell adhesion molecules. present crystallographic analysis the extracellular domain revealed an antiparallel arrangement molecules in crystal lattice. interface between two is asymmetric results a multimeric assembly. Structure-based mutagenesis site-directed photo-crosslinking analyses β4-mediated cell-cell that corresponds to trans homophilic interaction for assembly adhesion. This mode also...
Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 known as breast cancer type 1 susceptibility (BRCA1)-associated 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really (RING) zinc finger, ubiquitin-specific protease (UBP)-like finger (ZfUBP), and coiled-coil (CC). This architecture conserved orthologs; however, the domain's...
Activation of the nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) transcription factor, a central player in immune response regulation, is based on phosphorylation inhibitor kappaB alpha (IκBα) by Inhibitor kinase (IKK) that triggers IκBα degradation. Although beta (IκBβ) structurally similar to IκBα, its precise characteristics remain undefined. Herein, we report molecular interactivity IκBβ with kinase-active region IKK subunit 2 (IKK2), as well status, differs markedly...
Abstract The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT phosphorylated at threonine 249 during mitosis by serine/threonine kinase CDK1. Clinicopathological analyses revealed phosphorylation occurs more frequently advanced cancers. Using CRISPR/Cas9 genome editing, introduced substitution mutations endogenous locus found necessary for hTERT-mediated RNA dependent polymerase (RdRP)...