A5085675372- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- Chromosomal and Genetic Variations
- Wnt/β-catenin signaling in development and cancer
- Genomics and Phylogenetic Studies
- Retinal Development and Disorders
- Cancer-related Molecular Pathways
- Fungal and yeast genetics research
- Prostate Cancer Treatment and Research
- Glutathione Transferases and Polymorphisms
- Biotechnology and Related Fields
- Immunodeficiency and Autoimmune Disorders
- Genetic Syndromes and Imprinting
- Folate and B Vitamins Research
- Endometriosis Research and Treatment
- Neuroblastoma Research and Treatments
- Reproductive System and Pregnancy
- RNA regulation and disease
- Optical Imaging and Spectroscopy Techniques
Yamaguchi University
2018-2024
National Institute of Genetics
2014-2017
National University Cancer Institute, Singapore
2013-2014
National University of Singapore
2014
Tokyo University of Science
2003-2012
Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified characterized these based on publicly available datasets ChIP-Seq 97 factors (TFs) provided by ENCODE Roadmap Epigenomics projects. determined factor-binding sites (TFBSs) using TFBSs observed HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified....
We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression this protein. A total 387 cases were examined by immunohistochemistry; 72% NSCLC samples positive for SETDB1 staining, compared to 46% normal bronchial epithelium (106 cases) (p <0.0001). The percentage cells and intensity staining increased significantly with grade disease. Forced in lines enhanced their clonogenic growth vitro markedly tumour size a murine xenograft...
Abstract Background SOX7 is a transcription factor belonging to the SOX family. Its role in lung cancer unknown. Methods In this study, whole genomic copy number analysis was performed on series of non-small cell (NSCLC) lines and samples from individuals with epidermal growth receptor (EGFR) mutations using SNP-Chip platform. measured NSCLC lines, forced expressed one these lines. Results A notable surprise that numerous (CN) changes observed Asian, non-smoking EGFR mutant were nearly same...
Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism SNP on chromosome 9p21 endometriosis by leveraging "allele-specific" genomic approaches. By re-sequencing 1.29 Mb region and scrutinizing DNase-seq data from ENCODE project, prioritized rs17761446 as candidate...
Prostate cancer (PC) is the second most common in men. Family history major risk factor for PC. Only two susceptibility genes were identified PC, BRCA2 and HOXB13. A comprehensive search of germline variants patients with PC has not been reported Japanese families. In this study, we conducted exome sequencing followed by Sanger to explore responsible 140 from 66 addition known genes, HOXB13, TRRAP a mutually exclusive manner seven large families (three or four per family). We also found...
High-grade serous ovarian cancer (HGSOC) is the most aggressive histological type of epithelial cancer, which characterized by a high frequency somatic TP53 mutations. We performed exome analyses tumors and matched normal tissues 34 Japanese patients with HGSOC observed substantial number without mutation (24%, 8/34). Combined results copy variation analyses, we subdivided into subtypes designated ST1 ST2. showed intact p53 pathway was fewer mutations alterations. In contrast, impaired in...
Abstract MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted cell subsets largely unknown. Here, we report mice in which cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated immature thymocytes ( Bcl11b ∆iThy mice) develop chronic inflammation. lack conventional and whereas CD4 + IL-18R...
TdT interacting factor 1 (TdIF1) was identified as a protein that binds to terminal deoxynucleotidyltransferase (TdT) negatively regulate activity. is template-independent DNA polymerase catalyzes the incorporation of deoxynucleotides 3'-hydroxyl end templates increase junctional diversity immunoglobulin or T-cell receptor (TcR) genes. Here, using bioinformatics analysis, we binding, binding and dimerization regions, nuclear localization signal (NLS) in TdIF1. TdIF1 bound double-stranded...
Bood POZ containing gene type 2 (BPOZ-2), which contains ankyrin repeats, NLS, BTB/POZ domains and LXXLL motifs, is an adaptor protein for the E3 ubiquitin ligase scaffold CUL3. We isolated a cDNA encoding eukaryotic elongation factor 1A1 (eEF1A1) as BPOZ-2 binding by screening human thymus library using yeast two-hybrid system. eEF1A1 essential translation also involved in 26S proteasome-dependent degradation of misfolded or unfolded proteins. The between was confirmed pull-down...
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital absence of the vagina and uterus. We conducted genome-wide SNP analyses exome sequencing to detect causes MRKH syndrome. identified de novo variants MYCBP2, NAV3, PTPN3 in three families a variant MYCBP2 sporadic case. Here, we demonstrated partial genetic makeup Japanese
Terminal deoxynucleotidyltransferase (TdT) interacting factor 2 (TdIF2) is an acidic protein that binds to TdT. TdIF2 DNA and core histones contains acidic-amino acid-rich region in its C-terminus. It has therefore been suggested function as a histone chaperone within the nucleus. localized nucleolus HEK 293T cells, N-terminal (residues 1–234) C-terminal 606–756) regions were crucial for nucleolar localization. A chromatin immunoprecipitation (ChIP) assay showed associated with promoter of...
ABSTRACT Retinitis pigmentosa (RP) and macular dystrophy (MD) are characterized by gradual photoreceptor death in the retina often associated with genetic mutations, including those prominin-1 (Prom1) gene. Prom1-knockout (KO) mice recapitulate key features of these diseases light-dependent retinal degeneration constriction blood vessels. The mechanisms underlying such have remained unclear, however. We here analysed early events Prom1-KO mice. found that cell glial activation occur between...
DNA polymerase μ (pol μ) catalyzes nonhomologous end‐joining in double‐stranded break repair. Pol consists of an amino‐terminal BRCA 1 carboxyl‐terminal homology ( BRCT ) domain and a pol β‐like region, which contains the catalytic site. By cellulose column chromatography, using full‐length five different deletion mutants, we found that region has (ds )‐binding activity. without reduces polymerization activity when compared to μ. Observation by atomic force microscopy showed binds ends...
Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase that enhances the Ig and TcR gene diversity in N region at junctions of variable (V), (D) joining (J) segments B- T-cells. TdT synthesizes concert with many proteins including DNA-PKcs, Ku70 Ku86. To elucidate molecular mechanism synthesis, we first attempted to isolate genes products directly interact TdT.Using yeast two-hybrid system, isolated cDNA clone encoding novel nuclear protein interacts TdT. This was designated as...
Bood POZ containing gene type 2 (BPOZ-2) is involved in the growth suppressive effect of phosphatase and tensin homologue (PTEN). We showed that BPOZ-2 a human counterpart yeast Btb3p, which putative adaptor for Pcu3p-based ubiquitin ligase. bound to E3 ligase CUL3 vitro vivo. itself was ubiquitinated through CUL3-based mainly within nucleus degraded by 26S proteasome. Although expressed cytoplasm, it accumulated presence specific proteasome inhibitor MG132. may be recruited from cytoplasm....
N regions at the junction of V, D and J DNA segments are synthesized with large protein complexes including terminal deoxynucleotidyltransferase (TdT) during V(D)J recombination in B‐ or T‐cells. TdT directly binds to TdIF1, TdIF2, PCNA Ku70/86 heterodimer. Using a yeast two‐hybrid system, we isolated cDNA clone encoding gene for TReP‐132, which is involved P450scc expression steroid‐hormone‐producing cells lymphoid cells. Interaction between TReP‐132 TdIF1 was confirmed by pull‐down assay...
Aim: Bilirubin, a final degradation product of heme produced mainly in the spleen, is carried to liver through its binding albumin blood circulation. After transport hepatocytes, ligandin (glutathione S‐transferase; GST) carries bilirubin endoplasmic reticulum (ER). uridine 5'‐diphosphate‐glucuronosyltransferase 1A1 (UGT1A1) glucuronidates for solubilization ER. Methods: By GST pull‐down and co‐immunoprecipitation assays, GSTA2, member α‐class GST, was observed directly bind UGT1A1 region...
We isolated human cDNA clone encoding Bood POZ containing gene type 2 (BPOZ-2) as a with product that binds to TdT interacting factor 1 (TdIF1) using yeast two-hybrid system. BPOZ-2 is an adaptor for E3 ligase CUL3 and participates in developmental processes. The binding between TdIF1 was confirmed by GST pull-down immunoprecipitation assays specific antibodies against vitro vivo. Although when solely expressed COS7 cells, observed mainly within the cytoplasm, co-transfection of pEGFP-BPOZ-2...
Terminal deoxynucleotidyltransferase (TdT), which template-independently synthesizes DNA during V(D)J recombination in lymphoid cells, is ubiquitylated by a BPOZ-2/Cul3 complex, as the ubiquitin ligase, and then degraded 26 S proteasome. We show here that TdT Cul3-based ubiquitylation system vitro. Because could also be absence of Cul/BPOZ-2, we determined it directly E2 proteins UbcH5a/b/c UbcH6, E3-independently. Furthermore, inhibited its nucleotidyltransferase activity.
Mobile elements comprise about half of the human genome. Three active mobile element families (L1, Alu, and SVA) possibly cause diseases such as cancer. We conducted insertion (MEI) profiling 44 epithelial ovarian cancers using exome-sequencing data. identified a total 106 MEIs Mobster program, 8 which were novel exonic MEIs.
Long noncoding RNAs (lncRNAs) serve pivotal roles in cancer biology. The present study investigated the oncogenic of lncRNAs renal cell carcinoma (RCC) and their potential as prognostic biomarkers. lncRNA leucine‑rich repeat containing 75 A‑antisense RNA1 (LRRC75A‑AS1) was identified through microarray a that may predict efficacy immune checkpoint inhibitor therapy progression RCC. subsequently assessed expression LRRC75A‑AS1 212 patients with clear RCC (ccRCC) who underwent nephrectomy,...