A5058943390- Heat shock proteins research
- Fungal and yeast genetics research
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- thermodynamics and calorimetric analyses
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Metabolism and Genetic Disorders
- Enzyme Structure and Function
- Neurobiology and Insect Physiology Research
- Protein Structure and Dynamics
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Lipid metabolism and biosynthesis
- Physiological and biochemical adaptations
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Reactions
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Advanced Synthetic Organic Chemistry
- Invertebrate Immune Response Mechanisms
Shizuoka University
2014-2024
Kyoto University
2019-2023
Tokyo Metropolitan Institute of Medical Science
2002-2015
Massachusetts Institute of Technology
2006-2011
Frontier Science Foundation
2003-2004
Nippon Soken (Japan)
2004
Takara (Japan)
1997-1998
University of Chicago
1995-1997
Howard Hughes Medical Institute
1995-1997
Northwestern University
1997
The substrate-specific protein chaperone Hsp90 (heat shock 90) from Saccharomyces cerevisiae functions in diverse signal transduction pathways. A mutation YDJ1 , a member of the DnaJ family, was recovered synthetic-lethal screen with mutants. In an otherwise wild-type background, ydj1 exerted strong and specific effects on three substrates, derepressing two (the estrogen glucocorticoid receptors) reducing function third tyrosine kinase p60 v- src ). Analysis one these receptor, indicated...
Cdc37 is required for cyclin-dependent kinase activation and genetically linked with the activity of several other kinases, including oncogenic v-Src, casein II, MPS-1 kinase, sevenless. Strikingly, many pathways involving also involve protein chaperone Hsp90. The identification as 50-kD in Hsp90-kinase complexes, together data, led to recent suggestion that a kinase-targeting "subunit" We directly examined effect on Hsp90 functions. Rather than simply acting an accessory factor Hsp90,...
The majority of mouse HSP90 exists as alpha-alpha and beta-beta homodimers. Truncation the 15-kDa carboxy-terminal region by digestion with Ca(2+)-dependent protease m-calpain caused dissociation dimer. When expressed in a reticulocyte lysate, full-length human alpha formed dimeric form. A plasmid harboring cDNA was constructed so that 49 amino acid residues were removed when translated vitro. This carboxy-terminally truncated found to exist monomer. In contrast, loss 118 from terminus did...
Abstract Huntington’s disease is a neurodegenerative disorder resulting from expansion of polyglutamine tract in the Huntingtin protein. Mutant forms intracellular aggregates within neurons, although it unclear whether or more soluble protein represent pathogenic species. To examine link between aggregation and neurodegeneration, we generated Drosophila melanogaster transgenic strains expressing fluorescently tagged human huntingtin encoding (Q138) nonpathogenic (Q15) proteins, allowing vivo...
Article10 October 2019Open Access Transparent process Parkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomes Fumika Koyano Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Search for more papers by this author Koji Yamano Hidetaka Kosako Division Cell Signaling, Fujii Memorial Sciences, Tokushima University, Tokushima, Yoko Kimura Department Agriculture Graduate School Integrated Science and Technology, Shizuoka Shizuoka,...
Memory consolidation is augmented by repeated learning following rest intervals, which known as the spacing effect. Although effect has been associated with cumulative cellular responses in neurons engaged memory, here, we report neural circuit-based mechanism for generating memory-related mushroom body (MB) parallel circuits Drosophila To investigate activated during training, monitored expression of phosphorylation mitogen-activated protein kinase (MAPK), ERK [phosphorylation extracellular...
Valosin-containing protein (p97/VCP) has been proposed as playing crucial roles in a variety of physiological and pathological processes such cancer neurodegeneration. We previously showed that VCP(K524A), an ATPase activity-negative VCP mutant, induced vacuolization, accumulation ubiquitinated proteins, cell death, phenotypes commonly observed neurodegenerative disorders. However, any regulatory mechanism its activity not yet clarified. Here, we show oxidative stress readily inactivates...
p97/valosin-containing protein (VCP) is a member of the AAA family proteins, which plays various important roles in cells by using its ATPase activity. But mechanism regulating activity mostly unknown. We report here that VCP highly modified throughout via acetylation and phosphorylation. In addition to six previously identified phosphorylation sites, we at least 14 serines, threonines, 6 tyrosines 22 lysines as potential modification sites. Interestingly, these sites included Lys251 Lys524,...
VCP /p97 is a hexameric ring‐shaped AAA + ATP ase that participates in various ubiquitin‐associated cellular functions. Mis‐sense mutations gene are associated with the pathogenesis of two inherited diseases: inclusion body myopathy Paget's disease bone and front‐temporal dementia ( IBMPFD ) familial amyotrophic lateral sclerosis ALS ). These pathogenic s have higher affinities for several cofactors, including Npl4, Ufd1 p47. In Parkin‐dependent mitochondrial quality control systems,...
A new mode of herbicidal action was established by finding specific inhibitors imidazoleglycerol phosphate dehydratase, an enzyme histidine (His) biosynthesis. Three triazole phosphonates inhibited the reaction with Ki values 40 [plus or minus] 6.5, 10 1.6, and 8.5 1.4 nM, respectively, were highly cytotoxic to cultured plant cells. This effect completely reversed addition His, proving that cytotoxicity primarily caused inhibition His These showed wide-spectrum, postemergent activity at...
Yeast prions are protein-based genetic elements whose non-Mendelian patterns of inheritance explained by their altered conformations. Here we showed that aggregates made overexpression two different prion domains Sup35 and Rnq1, were stained in yeast thioflavin-S, an amyloid binding compound. These results suggested take the form vivo, supported idea self-propagating property amyloids is responsible for heritable traits prions.
Abstract When exposed to sublethal high temperatures, budding yeast cells can survive for a period of time; however, sufficient amount ubiquitin is necessary this survival. To understand the nature stress, we examined morphological changes in cells, focusing on vacuoles. Changes vacuolar morphology were notable, and ruffled membranes, accelerated invaginations vesicle-like formations observed. These occurred absence Atg1, Atg9 or Ivy1 but appeared require endosomal sorting proteins, such as...
Cellular heat stress can cause damage, and significant changes, to a variety of cellular structures. When exposed chronically high temperatures, yeast cells invaginate vacuolar membranes. In this study, we found that the expression Atg8, an essential autophagy factor, is induced after chronic stress. addition, without invaginations are conspicuously, beginning earlier invaginating vacuoles more frequently Our results indicate Atg8's invagination-suppressing functions do not require Atg8...
Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces formation, here we report that guanine monophosphate (cGMP) launches of unconsolidated in Drosophila. Genetic screening proteomic analyses showed neural activation the complex a histone H3K9 demethylase, Kdm4B, GMP synthetase, Bur, which is necessary sufficient memory. Kdm4B/Bur activated by phosphorylation through NO-dependent cGMP...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Inhibitors Imidazole Glycerol Phosphate DehydrataseIchiro Mori, Genji Iwasaki, Yoko Kimura, Shin-ichiro Matsunaga, Atsuko Ogawa, Toshihito Nakano, Hans-Peter Buser, Mika Hatano, Sachiyo Tada, and Kenji HayakawaCite this: J. Am. Chem. Soc. 1995, 117, 15, 4411–4412Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April...
Background Polyglutamine expansion in protein is responsible for several inherited neuro‐degenerative diseases. The has toxic effects on neural cells as well results forming aggregates. Using yeast, we examined the initial process of polyglutamine aggregate formation vivo . Results Following expression, tracts were a soluble form during lag period, and then formed insoluble complexes. was prolonged complex became slower by decreasing number treatment with guanidine hydrochloride. Gel...
Yeast Rfu1 (regulator for free ubiquitin chain 1) localizes to endosomes and plays a role in homeostasis by inhibiting the activity of Doa4. We show that Bro1, member class E vacuolar protein sorting proteins recruits Doa4 stimulates deubiquitinating activity, also involvement homeostasis. This recruitment was mediated direct interaction between region containing YPEL motif V domain which could be analogous mammalian Alix YPXnL motifs viral cellular proteins. Furthermore, overexpression...
At the primary structure level, 90-kDa heat shock protein (HSP90) is composed of three regions: N-terminal (Met1–Arg400), middle (Glu401–Lys615), and C-terminal (Asp621–Asp732) regions. In present study, we investigated potential subregion structures these regions their roles. Limited proteolysis revealed that region could be split into two fragments carrying residues Met1 to Lys281 (or Lys283) Glu282 Tyr284) Arg400. The former known carry ATP-binding domain. two-thirds (Glu401–Lys546)...
Amyloid‐like protein aggregates have been implicated in various diseases and the protein‐based inheritance of yeast prions. The molecular chaperone Hsp104 has shown to be necessary for aggregate formation polyglutamine yeast, maintenance several prion phenotypes through self‐propagating aggregates. In this paper, we show that are formed independently Hsp104, required efficiently produce more Similarly, [ PSI + ] system, Hsp104‐dependent epigenetic changes phenotype require presence normal...