A5088764876- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Crystallization and Solubility Studies
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
- Cancer-related gene regulation
- Animal Virus Infections Studies
- Heat shock proteins research
- Genetic Syndromes and Imprinting
- Cancer-related Molecular Pathways
- 14-3-3 protein interactions
- Pituitary Gland Disorders and Treatments
Tokyo Metropolitan Institute of Medical Science
2020-2025
Tokyo Institute of Technology
1984-2024
The University of Tokyo
2023
Nippon Medical School
2023
Tokyo Medical University
2023
Yamamoto Hospital
2023
Saiseikai Central Hospital
2019
University of Dundee
2013-2017
Cell Biotech (South Korea)
2016-2017
Japan Society for the Promotion of Science
2011
Article11 January 2017Open Access Transparent process Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress activation Shin-ichiro Hiraga Corresponding Author [email protected] orcid.org/0000-0002-8722-3869 Institute of Medical Sciences, School Medicine, Sciences & Nutrition, University Aberdeen, UK Search for more papers by this author Tony Ly Centre Gene Regulation Expression, Life Dundee, Javier Garzón Zuzana Hořejší The Francis Crick Institute,...
Stable inheritance of DNA methylation is critical for maintaining differentiated phenotypes in multicellular organisms. We have recently identified dual mono-ubiquitylation histone H3 (H3Ub2) by UHRF1 as an essential mechanism to recruit DNMT1 chromatin. Here, we show that PCNA-associated factor 15 (PAF15) undergoes UHRF1-dependent (PAF15Ub2) on chromatin a replication-coupled manner. This event will, turn, DNMT1. During early S-phase, preferentially ubiquitylates PAF15, whereas H3Ub2...
Small nucleolar RNAs (snoRNAs) function mainly as guides for the post-transcriptional modification of ribosomal (rRNAs). In recent years, several studies have identified a wealth small fragments (<35 nt) derived from snoRNAs (termed sdRNAs) that stably accumulate in cell, some which may regulate splicing or translation. A comparison human RNA deep sequencing data sets reveals box C/D sdRNA accumulation patterns are conserved across multiple cell types although ratio abundance different...
ABSTRACT Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They proposed to modulate mRNA translation stress responses. Here, we show the deubiquitylases USP5 USP13 recruited heat-induced granules. Heat-induced also contained K48- K63-linked ubiquitin chains. Depletion of or resulted in elevated chain levels accelerated assembly granules, suggesting these enzymes regulate stability through their...
K63-linked ubiquitin chains attached to plasma membrane proteins serve as tags for endocytosis and endosome-to-lysosome sorting. USP8 is an essential deubiquitinase the maintenance of endosomal functions. Prolonged depletion leads cell death, but major effects on cellular signaling pathways are poorly understood. Here, we show that causes aberrant accumulation endosomes induces immune stress responses. Upon depletion, two different decoders chains, TAB2/3 p62, were recruited activated...
The nucleolus is a subnuclear compartment and the site of ribosome biogenesis. Previous studies have implicated protein ubiquitylation in nucleolar activity. Here we show that USP36, deubiquitylating enzyme unknown function, regulates activity mammalian cells. USP36 localized to nucleoli via C-terminal region, which contains basic amino acid stretches. Dominant-negative inhibition caused accumulation ubiquitin-protein conjugates nucleoli, suggesting are action. deubiquitylated proteins...
Protein ubiquitylation is maintained by a dynamic balance of the conjugation and deconjugation ubiquitin. It remains unclear how deubiquitylation-stabilized substrates are directed for degradation. Branched ubiquitin chains promote substrate degradation through proteasome. TRIP12 UBR5 HECT-type E3 ligases, which specific lysine 29 (K29) 48 (K48) linkages, respectively. Here, we show that deubiquitylase (DUB) OTUD5 cooperatively modified UBR5, resulting in K29/K48 branched accelerated...
The lysosomal damage response is important for the maintenance of cellular homeostasis. Although mechanisms underlying repair and autophagic elimination damaged lysosomes have been elucidated, early signal transduction pathways genes induced in to remain elusive. We performed transcriptome proteome analyses found that TAB–TAK1–IKK–NF-κB axis activated by K63-linked ubiquitin chains accumulate on lysosomes. This activates expression various transcription factors cytokines promote...
Targeted protein degradation by proteolysis-targeting chimera (PROTAC) is one of the exciting modalities for drug discovery and biological discovery. It important to select an appropriate linker, E3 ligase ligand, a target ligand in development; however, it necessary synthesize large number PROTACs through trial error. Herein, using docking simulation ternary complex hematopoietic prostaglandin D synthase (H-PGDS) degrader, H-PGDS, cereblon, we have succeeded developing PROTAC(H-PGDS)-7 (6),...
The proteasome plays a central role in intracellular protein degradation. Age-dependent decline activity is associated with cellular senescence and organismal aging; however, the mechanism by which senescent cells remains elusive. Here, we show that nuclear foci contain exhibit liquid-like properties are formed cells. formation of senescence-associated (SANPs) dependent on ubiquitination RAD23B, similar to previously known foci, but also requires activity. RAD23B knockdown suppresses SANP...
The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure function of organelle. However, how localization regulated remains unknown. Here, we identified short stretch basic amino acids (RGKEKKIKKFKREKRR) resides C-terminal region serves as nucleolar signal for protein. We found this motif interacts central acidic nucleophosmin/B23,...
// Raffaella Pippa 1 , Ana Dominguez Raquel Malumbres Akinori Endo 2 Elena Arriazu 1, 3 Nerea Marcotegui Elizabeth Guruceaga and María D. Odero 3, 4 Hematology/Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain Centre Gene Regulation Expression, College Life Sciences, Dundee, UK Instituto de Investigación Sanitaria Navarra (IdiSNA), Department Biochemistry Genetics, Correspondence to: Odero, email: modero@unav.es Pippa, raffa80@gmail.com...
Endocytic trafficking is regulated by ubiquitylation (also known as ubiquitination) of cargoes and endocytic machineries. The role in lysosomal delivery has been well documented, but its the recycling pathway largely unknown. Here, we report that ubiquitin (Ub) ligase RFFL regulates regulators. An dominant-negative (DN) mutant induced clustering compartments (ERCs) delayed cargo without affecting traffic. A BioID interactome analysis revealed interacts with Rab11 effectors EHD1, MICALL1...
As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 is urgently required. We have developed a vaccine consisting attenuated vaccinia virus Dairen-I (DIs) strain platform carrying S gene (rDIs-S). rDIs-S induced neutralizing antibody T-lymphocyte responses in...
Abstract The molecular evolution processes underlying the acquisition of placenta in eutherian ancestors are not fully understood. Mouse NCK-interacting kinase (NIK)-related (NRK) is expressed highly and plays a role preventing placental hyperplasia. Here, we show NRK, which confers its function for inhibiting cell proliferation. Comparative genome analysis identified NRK orthologs across vertebrates, share citron homology (CNH) domains. Evolutionary revealed that underwent extensive amino...
Abstract Cells utilize diverse organelles to maintain homeostasis and respond extracellular stimuli. Recently, multifaceted aspects of organelle stress caused by various factors have been emerging. The endosome is an essential organelle, functioning as the central hub for membrane trafficking in cooperation with ubiquitin system. However, knowledge regarding endosomal stress, which refers endosome, currently limited. We recently revealed ubiquitin‐mediated early endosomes (EEs) its...
Abstract Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme involved in multiple membrane trafficking pathways. The activity inhibited by binding to 14-3-3 proteins. Mutations the 14-3-3-binding motif USP8 are related Cushing’s disease. However, molecular basis of regulation remains unclear. This study identified amino acids 645–684 as an autoinhibitory region, which might interact with catalytic USP domain, per results pull-down and single-molecule FRET assays performed this...