A5068692136- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Sirtuins and Resveratrol in Medicine
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
- Biochemical effects in animals
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Heat shock proteins research
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Inflammatory mediators and NSAID effects
- S100 Proteins and Annexins
- Genomics and Rare Diseases
- Protein Kinase Regulation and GTPase Signaling
- Fluorine in Organic Chemistry
- NF-κB Signaling Pathways
- Nanoplatforms for cancer theranostics
- Neonatal Respiratory Health Research
- Crystallography and molecular interactions
Pioneer (Japan)
2018-2023
RIKEN
2006-2023
Pioneer (United States)
2018-2022
Gladstone Institutes
2010-2016
University of California, San Francisco
2010-2016
The University of Tokyo
2006-2016
RIKEN Advanced Science Institute
2008-2012
Stress Protector During prolonged fasting, the oxidation of fatty acids leads to increased accumulation d -β-hydroxybutyrate (βOHB) in bloodstream. Such concentrations βOHB inhibit class I histone deacetylases. Histone acetylation turn influences transcriptional activity at various genes. Shimazu et al. (p. 211 , published online 6 December; see Perspective by Sassone-Corsi ) found that among genes showing transcription animals treated with high were two implicated cellular responses...
Although heat-shock protein 70 (HSP70), an evolutionarily highly conserved molecular chaperone, is known to be post-translationally modified in various ways such as phosphorylation, ubiquitination and glycosylation, physiological significance of lysine methylation has never been elucidated. Here we identify dimethylation HSP70 at Lys-561 by SETD1A. Enhanced was detected types human cancer immunohistochemical analysis, although the barely detectable corresponding non-neoplastic tissues....
Abstract Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- 3-methylhistidine (1MH 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is broad-specificity methyltransferase mediates formation of majority 1MH present mouse human proteomes. METTL9-catalyzed requires His-x-His (HxH) motif, where “x” preferably small amino acid,...
SIRT1 and SIRT3 are NAD+-dependent protein deacetylases that evolutionarily conserved across mammals. These proteins located in the cytoplasm/nucleus mitochondria, respectively. Previous reports demonstrated human deacetylates Acetyl-CoA Synthase 1 (AceCS1) cytoplasm, whereas homologous 2 (AceCS2) mitochondria. We recently showed 3-hydroxy-3-methylglutaryl CoA synthase (HMGCS2) is deacetylated by we demonstrate here (HMGCS1) cytoplasm. This novel pattern of substrate homology between...
Lysine methylation has been extensively studied in histones, where it shown to provide specific epigenetic marks for the regulation of gene expression; however, molecular mechanism and physiological function lysine proteins other than histones remains be fully addressed. To better understand substrate diversity methylation, S-adenosylmethionine (SAM) derivatives with alkyne-moieties have synthesized. A selenium-based SAM analog, propargylic Se-adenosyl-l-selenomethionine (ProSeAM), a wide...
Salicylate and acetylsalicylic acid are potent widely used anti-inflammatory drugs. They thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation NF-κB activity, direct activation AMPK. However, full spectrum activities is incompletely understood. Here we show that salicylate specifically inhibits CBP p300 lysine acetyltransferase activity in vitro by competition with acetyl-Coenzyme A at catalytic site. We a chemical...
G9a and the related enzyme GLP were originally identified as histone lysine methyltransferases then shown to also methylate several other non-histone proteins. Here, we performed a comprehensive screen identify their substrates in mouse embryonic stem cells (mESCs). We 59 proteins, including histones known substrates. One of substrates, activating transcriptional factor 7-interacting protein 1 (ATF7IP), is tri-methylated at H3 9 (H3K9)-like mimic by G9a/GLP complex, although this complex...
Cortactin is an F-actin-binding protein that localizes to the cell cortex, where actin remodeling required for migration occurs. We found cortactin shuttled between cytoplasm and nucleus under basal conditions. identified Kelch-like ECH-associated 1 (Keap1), a cytosolic involved in oxidant stress responses, as binding partner of promoted cortical localization migration. The ability promote regulated by various posttranslational modifications, including acetylation. showed acetylated form was...
Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a substrate. However, limited number of enzymes responsible for this modification have been reported. Moreover, the biological role has remained poorly understood to date. Here, we report that human METTL18 is methyltransferase ribosomal protein RPL3 specifically slows ribosome traversal Tyr codons, allowing proper folding synthesized proteins. By performing an in vitro assay with methyl...
Histidine (His) residues are methylated in various proteins, but their roles and regulation mechanisms remain unknown. Here, we show that carnosine N-methyltransferase 1 (CARNMT1), a known His methyltransferase of dipeptide (βAla-His), is major N1-position-specific methyltransferase. We found 52 sites 20 proteins underwent CARNMT1-mediated methylation. The consensus methylation site for CARNMT1 was identified as Cx(F/Y)xH, C3H zinc finger (C3H ZF) motif. CARNMT1-deficient catalytically...