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11.
Yoshinori Takahashi Megan M. Young Jacob M. Serfass Tsukasa Hori Hong-Gang Wang 《Autophagy》2013,9(7):1107-1109
Evasion of apoptosis, which enables cells to survive and proliferate under metabolic stress, is one of the hallmarks of cancer. We have recently reported that SH3GLB1/Bif-1 functions as a haploinsufficient tumor suppressor to prevent the acquisition of apoptosis resistance and malignant transformation during Myc-driven lymphomagenesis. SH3GLB1 is a membrane curvature-inducing protein that interacts with BECN1 though UVRAG and regulates the post-Golgi trafficking of membrane-integrated ATG9A for autophagy. At the premalignant stage, allelic loss of Sh3glb1 enhances Myc-induced chromosomal instability and results in the upregulation of anti-apoptotic proteins, including MCL1 and BCL2L1. Notably, we found that Sh3glb1 haploinsufficiency increases mitochondrial mass in overproliferated prelymphomatous Eμ-Myc cells. Moreover, loss of Sh3glb1 suppresses autophagy-dependent mitochondrial clearance (mitophagy) in PARK2/Parkin-expressing mouse embryonic fibroblasts (MEFs) treated with the mitochondrial uncoupler CCCP. Interestingly, PARK2-expressing Sh3glb1-deficient cells accumulate ER-associated immature autophagosome-like structures after treatment with CCCP. Taken together, we propose a model of mitophagy in which SH3GLB1 together with the class III phosphatidylinositol 3-kinase complex II (PIK3C3CII) (PIK3R4-PIK3C3-BECN1-UVRAG) regulates the trafficking of ATG9A-containing Golgi-derived membranes (A9+GDMs) to damaged mitochondria for autophagosome formation to counteract oncogene-driven tumorigenesis. 相似文献
12.
Kosuke Murakami Chie Kurihara Tomoichiro Oka Takashi Shimoike Yoshiki Fujii Reiko Takai-Todaka YoungBin Park Takaji Wakita Tsukasa Matsuda Ryota Hokari Soichiro Miura Kazuhiko Katayama 《PloS one》2013,8(6)
Human noroviruses (NoVs) are a major cause of non-bacterial gastroenteritis. Although histo-blood group antigens (HBGAs) have been implicated in the initial binding of NoV, the mechanism of that binding before internalization is not clear. To determine the involvement of NoVs and HBGAs in cell binding, we examined the localization of NoV virus-like particles (VLPs) and HBGAs in a human intestinal cell line and the human ileum biopsy specimens by immunofluorescence microscopy. The localizations of Ueno 7k VLPs (genogroup II.6) and each HBGA (type H1-, H2- and Leb-HBGAs) on the human intestinal cell line, Caco-2, were examined by confocal laser-scanning microscopy. To explore any interactions of NoVs and HBGAs in vivo, fresh biopsy specimens from human ileum were directly incubated with NoV VLPs and examined by immunofluorescence microscopy. We found that VLP binding depended on the state of cell differentiation, but not on the presence of HBGAs. In differentiated Caco-2 cells, we detected no type H1 HBGAs, but VLPs bound to the cells anyway. We incubated fresh biopsies of human ileum directly with VLPs, a model that better replicates the in vivo environment. VLPs mainly bound epithelial cells and goblet cells. Although the incubations were performed at 4°C to hinder internalization, VLPs were still detected inside cells. Our results suggest that VLPs utilize molecule(s) other than HBGAs during binding and internalization into cells. 相似文献
13.
Akemi Shodai Toshifumi Morimura Akemi Ido Tsukasa Uchida Takashi Ayaki Rina Takahashi Soichiro Kitazawa Sakura Suzuki Mikako Shirouzu Takanori Kigawa Yutaka Muto Shigeyuki Yokoyama Ryosuke Takahashi Ryo Kitahara Hidefumi Ito Noriko Fujiwara Makoto Urushitani 《The Journal of biological chemistry》2013,288(21):14886-14905
Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological signature of amyotrophic lateral sclerosis (ALS). Although accumulating evidence suggests the involvement of RNA recognition motifs (RRMs) in TDP-43 proteinopathy, it remains unclear how native TDP-43 is converted to pathogenic forms. To elucidate the role of homeostasis of RRM1 structure in ALS pathogenesis, conformations of RRM1 under high pressure were monitored by NMR. We first found that RRM1 was prone to aggregation and had three regions showing stable chemical shifts during misfolding. Moreover, mass spectrometric analysis of aggregated RRM1 revealed that one of the regions was located on protease-resistant β-strands containing two cysteines (Cys-173 and Cys-175), indicating that this region served as a core assembly interface in RRM1 aggregation. Although a fraction of RRM1 aggregates comprised disulfide-bonded oligomers, the substitution of cysteine(s) to serine(s) (C/S) resulted in unexpected acceleration of amyloid fibrils of RRM1 and disulfide-independent aggregate formation of full-length TDP-43. Notably, TDP-43 aggregates with RRM1-C/S required the C terminus, and replicated cytopathologies of ALS, including mislocalization, impaired RNA splicing, ubiquitination, phosphorylation, and motor neuron toxicity. Furthermore, RRM1-C/S accentuated inclusions of familial ALS-linked TDP-43 mutants in the C terminus. The relevance of RRM1-C/S-induced TDP-43 aggregates in ALS pathogenesis was verified by immunolabeling of inclusions of ALS patients and cultured cells overexpressing the RRM1-C/S TDP-43 with antibody targeting misfolding-relevant regions. Our results indicate that cysteines in RRM1 crucially govern the conformation of TDP-43, and aberrant self-assembly of RRM1 at amyloidogenic regions contributes to pathogenic conversion of TDP-43 in ALS. 相似文献
14.
Tsukasa Mizuhara Shinya Oishi Hiroaki Ohno Kazuya Shimura Masao Matsuoka Nobutaka Fujii 《Bioorganic & medicinal chemistry》2013,21(7):2079-2087
To investigate the mechanism of action of the potent antiviral compound PD 404182, three novel photoaffinity probes equipped with a biotin or alkyne indicator were designed and synthesized based on previous structure–activity relationship studies. These probes retained the potent anti-HIV activity of the original pyrimidobenzothiazine derivatives. In photoaffinity labeling studies using HIV-1-infected H9 cells (H9IIIB), eight potential proteins were observed to bind PD 404182. 相似文献
15.
16.
Shohei Sakuda Akira Isogai Tsukasa Makita Shogo Matsumoto Koshi Koseki Hisashi Kodama 《Bioscience, biotechnology, and biochemistry》2013,77(12):3251-3259
The structures of allosamidin (1) and methylallosamidin (2), novel insect chitinase inhibitors, were elucidated as 1 and 2 by acid hydrolysis experiments and analyses of 2d-NMR spectra. They are unique basic pseudotrisaccharides consisting of 2-acetamido-2-deoxy-d-allose (N-acetyl-d- allosamine) and a novel aminocyclitol derivative (3), termed allosamizoline. 相似文献
17.
Tsukasa Ikemura Akane Miyaji Hideaki Kashima Yuji Yamaguchi Naoyuki Hayashi 《Journal of physiological anthropology》2013,32(1):23
Background
Heat stress induces various physiological changes and so could influence ocular circulation. This study examined the effect of heat stress on ocular blood flow.Findings
Ocular blood flow, end-tidal carbon dioxide (PETCO2) and blood pressure were measured for 12 healthy subjects wearing water-perfused tube-lined suits under two conditions of water circulation: (1) at 35°C (normothermia) for 30 min and (2) at 50°C for 90 min (passive heat stress). The blood-flow velocities in the superior temporal retinal arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow in the STRA and SNRA was calculated from the integral of a cross-sectional map of blood velocity. PETCO2 was clamped at the normothermia level by adding 5% CO2 to the inspired gas. Passive heat stress had no effect on the subjects’ blood pressures. The blood-flow velocity in the RCV was significantly lower after 30, 60 and 90 min of passive heat stress than the normothermic level, with a peak decrease of 18 ± 3% (mean ± SE) at 90 min. Blood flow in the STRA and SNRA decreased significantly after 90 min of passive heat stress conditions, with peak decreases of 14 ± 3% and 14 ± 4%, respectively.Conclusion
The findings of this study suggest that passive heat stress decreases ocular blood flow irrespective of the blood pressure or arterial partial pressure of CO2. 相似文献18.
Takahiro Shiga Yoshifumi Kimira Hiroshi Mano Tetsunori Kawata Tadahiro Tadokoro Tsukasa Suzuki 《Bioscience, biotechnology, and biochemistry》2016,80(3):510-513
Vitamin B12 deficiency is a risk factor for bone disorders via mechanisms not fully understood. In this study, an increase in serum inorganic phosphorus (Pi) concentrations was associated with a vitamin B12 deficiency. Napi2a, a renal cotransporter for Pi reabsorption, accumulated on plasma membranes in a vitamin B12 deficiency suggests that vitamin B12 plays an important role in Pi homeostasis. 相似文献
19.
Hideyuki Yoshida Caleb A. Lareau Ricardo N. Ramirez Samuel A. Rose Barbara Maier Aleksandra Wroblewska Fiona Desland Aleksey Chudnovskiy Arthur Mortha Claudia Dominguez Julie Tellier Edy Kim Dan Dwyer Susan Shinton Tsukasa Nabekura YiLin Qi Bingfei Yu Michelle Robinette Christophe Benoist 《Cell》2019,176(4):897-912.e20
20.
Yuko Kitagawa Shinji Shimodera Fumiharu Togo Yuji Okazaki Atsushi Nishida Tsukasa Sasaki 《PloS one》2014,9(9)