A5007509548- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Kruppel-like factors research
- Fibroblast Growth Factor Research
- Biochemical and Molecular Research
- Genomics, phytochemicals, and oxidative stress
- Cancer-related gene regulation
- Genomics and Rare Diseases
- Metal Alloys Wear and Properties
- Energy and Environment Impacts
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Materials Engineering and Processing
- Lipid metabolism and biosynthesis
- Acute Myeloid Leukemia Research
- Advanced materials and composites
- Ovarian cancer diagnosis and treatment
Juntendo University
2020-2023
Niigata University
2014-2021
Tokyo Metropolitan Institute of Medical Science
2013-2016
Tohoku University
2013
The ubiquitin-proteasome system and autophagy are crucially important for proteostasis in cells. These pathways interdependent, dysfunction either pathway causes accumulation of ubiquitin-positive aggregates, a hallmark human pathological conditions. To elucidate vivo compensatory action(s) against proteasomal dysfunction, we developed mice with reduced proteasome activity their livers. mutant exhibited severe liver damage, accompanied by formation aggregates positive ubiquitin p62/Sqstm1,...
The post-translational modification of proteins through the addition UFM1, also known as ufmylation, plays a critical developmental role revealed by studies in animal models. recent finding that biallelic mutations UBA5 (the E1-like enzyme for ufmylation) cause severe early-onset encephalopathy with progressive microcephaly implicates ufmylation human brain development. More recently, homozygous UFM1 variant was proposed candidate aetiology microcephaly. Here, we establish locus based on two...
Protein modification by ubiquitin-like proteins (UBLs) amplifies limited genome information and regulates diverse cellular processes, including translation, autophagy antiviral pathways. Ubiquitin-fold modifier 1 (UFM1) is a UBL covalently conjugated with intracellular through ufmylation, reaction analogous to ubiquitylation. Ufmylation involved in processes such as endoplasmic reticulum (ER)-associated protein degradation, ribosome-associated quality control at the ER ER-phagy. However, it...
Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein covalently conjugated with intracellular proteins through ufmylation, similar to ubiquitylation. Ufmylation involved in processes such as endoplasmic reticulum (ER)-associated degradation, ribosome-associated quality control (RQC) at the ER (ER-RQC), and ER-phagy. However, it remains unclear how ufmylation regulates distinct ER-related functions. Here, we provide insights into mechanism of UFM1 E3 complex not only but also ER-RQC....
Upon infection of a cell by Salmonella , p62/Sqstm1 assembles on the microbes; simultaneously, is phosphorylated at Ser351, leading to inactivation Keap1, which responsible for degrading Nrf2. Thus, cytoprotective Nrf2 targets are induced same time that autophagosomes entrap microbes (xenophagy). However, detailed role during xenophagy has remained unclear. Here we show translocation invasive precedes Ser351 phosphorylation. Furthermore, in addition phosphorylation, oligomerization also...
We previously found that therapeutic targetable fusions are detected across various cancers. To identify fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cancer samples. 445 high confidence transcripts and identified four samples harbored FGFR3-TACC3 as an attractive target. The frequency of FGFR3-TACC3-fusion-positive is also 1.9% (2/103) independent cohort. Continuous expression the...
UBA5 is the activating enzyme of UFM1 in ufmylation post-translational modification system. Different neurological phenotypes have been associated with pathogenic variants including epilepsy, intellectual disability, movement disorders and ataxia.We describe a large multigenerational consanguineous family presenting severe congenital neuropathy causing early death infancy. Whole exome sequencing linkage analysis identified novel homozygous NM_024818.3 c.31C>T (p.Arg11Trp) mutation. Protein...
Early infantile epileptic encephalopathy-44 (EIEE44, MIM: 617132) is a previously described condition resulting from biallelic variants in UBA5 , gene involved ubiquitin-like post-translational modification system called UFMylation. Here we report five children four families with pathogenic . All presented global developmental delay, epilepsy, axial hypotonia, appendicular hypertonia, and movement disorder, including dystonia four. Affected individuals all have compound heterozygous the...
A germ line copy number duplication of chromosome 14q32, which contains ATG2B and GSKIP, was identified in families with myeloproliferative neoplasm (MPN). Here, we show that mice lacking both Atg2b Gskip, but not either alone, exhibited decreased hematopoiesis, resulting death utero accompanied by anemia. In marked contrast to MPN patients the hematopoietic stem cells (HSCs), particular long-term HSCs, double-knockout fetal livers significantly due increased cell death. Although remaining...
Summary Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein covalently conjugated with intracellular proteins through ufmylation, similar to ubiquitylation. Ufmylation involved in processes such as endoplasmic reticulum (ER)-associated degradation, ribosome-associated quality control (RQC) at the ER (ER-RQC), and ER-phagy. However, it remains unclear how ufmylation regulates distinct ER-related functions. Herein, we provide insights into mechanism of UFM1 E3 complex not only but...
Abstract Uterine cervical cancer is one of the most common in women worldwide, and prognosis advanced or recurrent cases remains poor because no effective molecular target therapies for this disease. The aim our study to identify validate therapeutically targetable gene fusions uterine cancer, leading development new therapeutic strategies. We have analyzed RNA sequencing data 253 TCGA samples search by using PRADA algorithm, validated Japanese dataset (n = 100) RT-PCR sanger sequencing. In...