A5023835566- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Cancer Cells and Metastasis
- Liver Disease Diagnosis and Treatment
- FOXO transcription factor regulation
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Protein Kinase Regulation and GTPase Signaling
- Digestive system and related health
- Advanced Proteomics Techniques and Applications
- Autophagy in Disease and Therapy
- T-cell and B-cell Immunology
- Enzyme function and inhibition
- Telomeres, Telomerase, and Senescence
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Chemokine receptors and signaling
- Protease and Inhibitor Mechanisms
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Renal and related cancers
- Protein Degradation and Inhibitors
Kyushu University
2011-2023
Nagoya City University
2018-2020
Cell Biotech (South Korea)
2015
Japan Science and Technology Agency
2011
Kyoto University
2010
C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)-κB signaling pathway, regulation of production cells remained unclear. We have identified a noncanonical pathway for that is mediated by mammalian target rapamycin complex 1 (mTORC1) but independent NF-κB. Multiple phosphoproteomics approaches transcription forkhead box K1 (FOXK1) as downstream mTORC1. Activation...
The mechanistic target of rapamycin complex 1 (mTORC1) plays a central role in regulating cell growth and metabolism by responding to cellular nutrient conditions. activity mTORC1 is controlled Rag GTPases, which are anchored lysosomes via Ragulator, pentameric protein consisting membrane-anchored p18/LAMTOR1 two roadblock heterodimers. Here we report the crystal structure Ragulator with domains RagA-C, helps elucidate molecular basis for regulation GTPases. In structure, p18 wraps around...
Endosome maturation depends on membrane contact sites (MCSs) formed between endoplasmic reticulum (ER) and endolysosomes (LyLEs). The mechanism underlying lipid supply for this process its pathophysiological relevance remains unclear, however. Here, we identify PDZD8-the mammalian ortholog of a yeast ERMES subunit-as protein that interacts with protrudin, which is located at ER-LyLE MCSs. Protrudin PDZD8 promote the formation MCSs, shows ability to extract various lipids from ER....
Abstract Although the mammalian intestinal epithelium manifests robust regenerative capacity after various cytotoxic injuries, underlying mechanism has remained unclear. Here we identify cyclin-dependent kinase inhibitor p57 as a specific marker for quiescent cell population located around +4 position of crypts. Lineage tracing reveals that + cells serve enteroendocrine/tuft precursors under normal conditions but dedifferentiate and act facultative stem to support regeneration injury....
D-type cyclins play a pivotal role in G(1)-S progression of the cell cycle, and their expression is frequently deregulated cancer. Cyclin D1 has half-life only ~30 min as result its ubiquitylation proteasomal degradation, with various F-box proteins, including Fbxo4, Fbxw8, Skp2, Fbxo31, having been found to contribute ubiquitylation. We have now generated Fbxo4-deficient mice no abnormalities these animals. accumulation was thus not observed Fbxo4(-/-) mouse tissues. The cyclin embryonic...
Dormant cancer cells known as disseminated tumor (DTCs) are often present in bone marrow of breast patients. These DTCs thought to be responsible for the incurable recurrence cancer. The mechanism underlying long-term maintenance remains unclear, however. Here, we show that Fbxw7 is essential dormancy. Genetic ablation disrupted quiescence DTCs, rendering them proliferative, mouse xenograft and allograft models. Fbxw7-deficient were significantly depleted by treatment with paclitaxel,...
Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder caused by overnutrition and can lead to nonalcoholic steatohepatitis (NASH) hepatocellular carcinoma (HCC). The transcription factor Forkhead box K1 (FOXK1) implicated in regulation of lipid metabolism downstream mechanistic target rapamycin complex 1 (mTORC1), but its role NAFLD-NASH pathogenesis understudied. Here, we show that FOXK1 mediates nutrient-dependent suppression catabolism the liver. Hepatocyte-specific...
Caspases are central to apoptosis, and the principal executioner caspases, caspase-3 -7, were reported be similar in activity, primary structure, three-dimensional structure. Here, we identified different activity -7 within cells examined relationship between their structure function using human expressing almost equal amounts of exogenous caspase-3, caspase-7, and/or chimeric constructs after down-regulation endogenous expression. Caspase-3 (produced cells) showed much stronger cleaving...
Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 activated on lysosomal membrane induces phosphorylation variety downstream molecules. We previously showed that protein phosphatase 2A (PP2A)-mediated dephosphorylation transcription factor forkhead box K1 (FOXK1). The mechanism underlying signal transduction from cytoplasmic nuclear FOXK1 has remained unclear, however, we...
All trophoblast subtypes of the placenta are derived from stem cells (TSCs). TSCs have capacity to self-renew, but how proliferation these is regulated in undifferentiated state has been largely unclear. We now show that F-box protein Skp2 regulates and thereby plays a pivotal role placental development mice on C57BL/6 background. The Skp2-/- mouse embryos background was smaller than their Skp2+/+ littermates, with mutant also manifesting intrauterine growth retardation. Although were born...
Developing CD4+CD8+ double-positive (DP) thymocytes with randomly generated T cell receptors (TCRs) undergo positive (maturation) or negative (apoptosis) selection on the basis of strength TCR stimulation. Selection fate is determined by engagement ligands a subtle difference in affinity, but molecular details signaling leading to different outcomes have remained unclear. We performed phosphoproteome analysis DP and found that p90 ribosomal protein kinase (RSK) phosphorylation at Thr562 was...