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Institution

Kyushu University

EducationFukuoka, Japan
About: Kyushu University is a education organization based out in Fukuoka, Japan. It is known for research contribution in the topics: Population & Catalysis. The organization has 68284 authors who have published 135190 publications receiving 3055928 citations. The organization is also known as: Kyūshū Daigaku.


Papers
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Journal ArticleDOI
TL;DR: Domain-swapping analyses showed that the specificity of interaction of VHL-box and SOCS-box proteins with Cullin-Rbx modules is determined by the Cul2 and Cul5 boxes, respectively, which suggest that the functions of the Cul1-rbx1 and Cul2-R bx2 modules are distinct.
Abstract: The ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein) complex is a member of a family of ubiquitin ligases that share a Cullin-Rbx module. SOCS-box proteins recruit substrates to the ECS complex and are linked to Cullin-Rbx via Elongin B/C. VHL has been implicated as a SOCS-box protein, but lacks a C-terminal sequence (downstream of the BC box) of the SOCS box. We now show that VHL specifically interacts with endogenous Cul2-Rbx1 in mammalian cells, whereas SOCS-box proteins associate with Cul5-Rbx2. We also identify LRR-1 and FEM1B as proteins that share a region of homology with VHL (the VHL box, including the BC box and downstream residues) and associate with Cul2-Rbx1. ECS complexes can thus be classified into two distinct protein assemblies, that is, those that contain a subunit with a VHL box (composed of the BC box and a downstream Cul2 box) that interacts with Cul2-Rbx1, and those that contain a subunit with a SOCS box (BC box and downstream Cul5 box) that interacts with Cul5-Rbx2. Domain-swapping analyses showed that the specificity of interaction of VHL-box and SOCS-box proteins with Cullin-Rbx modules is determined by the Cul2 and Cul5 boxes, respectively. Finally, RNAi-mediated knockdown of the Cul2-Rbx1 inhibited the VHL-mediated degradation of HIF-2alpha, whereas knockdown of Cul5-Rbx2 did not affect it. These data suggest that the functions of the Cul2-Rbx1 and Cul5-Rbx2 modules are distinct.

471 citations

Journal Article
TL;DR: A method by which immunoperoxidase staining can be applied to formalin-fixed, paraffin-embedded tissue sections to demonstrate amyloid deposits in cerebral and systemic amyloidsotic tissues is designed.

471 citations

Journal ArticleDOI
TL;DR: A novel role of γδ T cells as a first line of host defense controlling neutrophil-mediated innate immune responses is demonstrated, which is generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses.
Abstract: Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that γδ T cell population was the major source of IL-17. Mice depleted of γδ T cells by mAb treatment or mice genetically lacking Vδ1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vδ1+ γδ T cells as the source of IL-17. It was further revealed that γδ T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although γδ T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of γδ T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.

471 citations

Journal ArticleDOI
TL;DR: The design of an aromatic molecule based on a spiro-acridine derivative leads to an organic light-emitting diode (OLED) that rivals phosphorescent devices regarding exciton generation efficiency.
Abstract: Make your OLED fluorescent: an aromatic molecule based on a spiro-acridine derivative was designed, and its photoluminescence and electroluminescence were characterized. By combining the donor and acceptor moieties a small energy gap between the lowest singlet and triplet states was achieved. This design leads to an organic light-emitting diode (OLED) that rivals phosphorescent devices regarding exciton generation efficiency.

471 citations

Journal ArticleDOI
TL;DR: It is suggested that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy.
Abstract: Glioblastoma (GBM) is the most malignant brain tumor and is highly resistant to intensive combination therapies and anti-VEGF therapies. To assess the resistance mechanism to anti-VEGF therapy, we examined the vessels of GBMs in tumors that were induced by the transduction of p53+/− heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. We were surprised to observe GFP+ vascular endothelial cells (ECs). Transplantation of mouse GBM cells revealed that the tumor-derived endothelial cells (TDECs) originated from tumor-initiating cells and did not result from cell fusion of ECs and tumor cells. An in vitro differentiation assay suggested that hypoxia is an important factor in the differentiation of tumor cells to ECs and is independent of VEGF. TDEC formation was not only resistant to an anti-VEGF receptor inhibitor in mouse GBMs but it led to an increase in their frequency. A xenograft model of human GBM spheres from clinical specimens and direct clinical samples from patients with GBM also showed the presence of TDECs. We suggest that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy.

470 citations


Authors

Showing all 68546 results

NameH-indexPapersCitations
Tony Hunter175593124726
Stanley B. Prusiner16874597528
Yang Yang1642704144071
Stephen J. Elledge162406112878
Takashi Taniguchi1522141110658
Andrew White1491494113874
Junji Tojo13587884615
Claude Leroy135117088604
Georges Azuelos134129490690
Susumu Oda13398180832
Lucie Gauthier13267964794
Hiroshi Sakamoto131125085363
Frank Caruso13164161748
Kiyotomo Kawagoe131140690819
Kozo Kaibuchi12949360461
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023137
2022479
20214,870
20205,014
20194,902
20184,570