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Research at OU


71  Ito, T.; Fujio, Y.; Takahashi, K.; Azuma, J.
(Graduate School of Pharmaceutical Sciences)
Degradation of NFAT5, a Transcriptional Regulator of Osmotic Stress-Related Genes, is a Critical Event for Doxorubicin-Induced Cytotoxicity in Cardiac Myocytes
The Journal of Biological Chemistry, 282, 1152-60 (2007)

NFAT5, a novel member of the NFAT family proteins, functions as a transcriptional factor responsible for the adaptation to hyperosmotic stress. In this paper, we found that anti-cancer drug doxorubicin which is also known as a cardiotoxic agent enhances the degradation of NFAT5 through the proteasome activation and downregulates its targeted genes in cultured cardiomyocytes. Inhibition of NFAT5 by using either dominant-negative form of NFAT5 or siRNA decreased myocyte viability. Thus, NFAT5 is a positive regulator of cardiomyocyte survival.

72 Iwata, K.; Fujiwara, T.; Matsuki, Y.; Akutsu, H.; Takahashi, S.; Naiki, H.; Goto, Y.
(Institute for Protein Research)
3D Structure of Amyloid Protofilaments of β2-Microglobulin Fragment Probed by Solid-State NMR
Proceeding of the National Academy of Sciences of the United States of America, 103, 18119-18124 (2006)

73 Kamada, K.; Kubota, Y.*1; Arata, T.*1; Shindo, Y.*1; Hanaoka, F.*2
*1(Graduate School of Science)
*2(Graduate School of Frontier Biosciences)
Structure of the Human GINS Complex and Its Assembly and Functional Interface in Replication Initiation
Nature Structural & Molecular Biology, 14, 388-396 (2007)

The eukaryotic GINS complex is composed of four subunits, Sld5, Psf1, Psf2 and Psf3, and is essential for the establishment of DNA replication forks and replisome progression. Crystallographic work showed that they pack together into a two-layered trapezoid structure, with Sld5 and Psf1 on one level above Psf2 and Psf3 respectively on the other. The data suggest that the core complex ensures a stable platform for the C-terminal domain of Psf1 to act as a key interaction interface for other proteins in the replication-initiation process.

74 Kaneko, R.; Kato, H.; Kawamura, Y.; Esumi, S.; Hirayama, T.; Hirabayashi, T.; Yagi, T.
(Graduate School of Frontier Biosciences)
Allelic Gene Regulation of Pcdh-α and -γ Clusters Involving Both Monoallelic and Biallelic Expression in Single Purkinje Cells
The Journal of Biological Chemistry, 281, 30551-30560 (2006)

The Pcdh-α and –γ genes encode multiple transmembrane proteins. We investigated total allelic gene regulation in the Pcdh-α and –γ clusters in single Purkinje cells. Using split single-cell RT-PCR analysis, almost all of the Purkinje cells biallelically expressed all the C-type isoforms, whereas the Pcdh-α, -γA and –γB isoforms showed both monoallelic and combinatorial expression. The multiple gene regulations in the Pcdh-α and -γ clusters had a potential mechanism for increasing the diversity of individual neurons in the brain.

75 Kitamura, H.; Morikawa, H.*1; Kamon, H.*2; Iguchi, M.*2; Hojyo, S.*1; Fukada, T.*1; Yamashita, S.*2; Kaisho, T.*1; Akira, S.*1, 2;Murakami, M.*1, 2; Hirano, T.*1, 2
*1(Graduate School of Medicine)
*2(Graduate School of Frontier Bioscience)
Toll-Like Receptor-Mediated Regulation of Zinc Homeostasis Influences Dendritic Cell Function
Nature Immunology, 7, 971-977 (2006)

76 Kurihara, D.; Matsunaga, S.; Kawabe, A.; Fujimoto, S.; Noda, M.; Uchiyama, S.; Fukui, K.
(Graduate School of Engineering)
Aurora Kinase is Required for Chromosome Segregation in Tobacco BY-2 Cells
The Plant Journal, 48, 572-580 (2006)

77 Kurooka, M.; Kaneda, Y.
(Graduate School of Medicine)
Inactivated Sendai Virus Particles Eradicate Tumors by Inducing Immune Responses through Blocking Regulatory T Cells
Cancer Research, 67, 227-236 (2007)

We report that inactivated Sendai virus particle (HVJ-E) solely has vigorous anti-tumor effects. Intra-tumor injections of HVJ-E eradicated tumors in 60-80 % of mice. With HVJ-E, dendritic cells (DCs) were maturated, immune cells were infiltrated into tumor bed, and tumor-specific cytotoxic T lymphocytes were activated. Moreover, IL-6 secreted from HVJ-E-stimulated DCs rescued effector T cell proliferation from regulatory T cell (Treg)-mediated suppression. Thus, by both enhancing anti-tumor immunity and attenuating Treg-mediated suppression, HVJ-E may open the way for effective cancer immunotherapy.

78 Maeda, Y.; Tashima, Y.; Houjou, T.; Fujita, M.; Yoko-o, T.; Jigami, Y.; Taguchi, R.; Kinoshita, T.
(Research Institute for Microbial Diseases)
Fatty Acid Remodeling of GPI-anchored Proteins Is Required for Their Raft Association
Molecular Biology of the Cell, 18, 1497-1506 (2007)

The nature that GPI-anchored proteins (APs) are enriched into lipid rafts is critical, because rafts modulate various biological functions of GPI-APs. How are GPI-APs accumulated in rafts? Here we report that GPI-APs become competent to be incorporated into lipid rafts by PGAP3- and PGAP2-mediated fatty acid remodeling, replacement of the unsaturated chain with saturated one in PI moiety. The remodeling occurs most likely in the Golgi and requires the preceding PGAP1-mediated deacylation from inositol of GPI-APs in the ER.

79 Mohri, T.; Tanaka, H.; Tajima, G.; Kajino, K.; Sonoi, H.; Hosotsubo, H.; Ogura, H.; Kuwagata, Y.; Shimazu, T.; Sugimoto, H.
(Graduate School of Medicine)
Synergistic Effects of Recombinant Human Soluble Thrombomodulin and Fluid-Volume Resuscitation in a Rat Lethal Crush Injury Model
Shock, 26, 581-586 (2006)

Severe crush injury results in a high mortality rate due to acute circulatory failure and hyperkalemia. We evaluated whether administration of prophylactic recombinant human soluble thrombomodulin (rhsTM) and/or fluid volume resuscitation prior to reperfusion attenuates severe crush injury in rats, whose both hindlimbs were compressed. Combined administration of rhsTM and volume resuscitation significantly decreased hemoconcentration and hyperkalemia, and also improved the serum interleukin-6 level and mortality. We propose that this prophylactic combined therapy may be effective for severe crush injury patients.

80 Murakami, S.*1; Nakashima, R.*1; Yamashita. E.*2; Matsumoto. T.*1; Yamaguchi. A.*1
*1(Institute of Scientific and Industrial Research)
*2(Institute for Protein Research)
Crystal Structures of a Multidrug Transporter Reveal a Functionally Rotating Mechanism
Nature, 443, 173-179 (2006)
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