記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Phycology  

We investigated the phylogenetic relationships and the taxonomy of 20 sarcinoid strains by their morphological features and using 18S rDNA sequence data. Nineteen strains of Chlorosarcinopsis (Gerneck) Herndon and allied genera were divided into four groups (A-D). Group A, comprising eight species, was concordant with the description of Chlorosarcinopsis and divided into four polyphyletic subgroups. Group B included two species of Chlorosarcinopsis and two strains of Desmotetra stigmatica (Deason) Deason et Floyd, all of which had parallel thylakoid membranes in pyrenoid matrices, and zoospores bearing apical stigma and subapical flagellar apparatus. The definition of Desmotetra Deason et Floyd was emended to include these features, and Chlorosarcinopsis delicata S. Watanabe was transferred to this genus. Group C comprised Chlorosarcina stigmatica Deason (ASIB.T105), for which we proposed Sarcinochlamys gen. nov., a genus distinct from Chlorosarcina Gerneck in having walled zoospores. Group D, comprising six species, corresponded to Neochlorosarcina and was divided into two subgroups. The presence of thin cell walls in Neochlorosarcina S. Watanabe was ascertained as a valid feature for circumscribing the sarcinoid genera. The physiological experiments on the species of Chlorosarcinopsis and Chlorosarcina by Groover and Bold (1968) were assessed based on the phylogenetic results. Groups (A, B, D) were roughly characterized by these features: algal mass color, utilization of selected nitrogen compounds and carbon sources under light/dark and aerobic/anaerobic conditions, and requirement for vitamin B12. Molecular analysis revealed that Chlorosphaeropsis alveolata Herndon had closer affinity with solitary Protosiphon Klebs and Spongiochloris Starr than with sarcinoid members. © 2005 Phycological Society of America.

DOI： 10.1111/j.1529-8817.2006.00196.x

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical and Biophysical Research Communications  

Cyclin E-Cdk2 is an evolutionary conserved cyclin-dependent kinase (CDK) complex that drives the G1 to S phase transition of the cell cycle. A novel cDNA encoding a HECT family protein also containing RCC1-like repeats was isolated by a yeast two-hybrid screening using both cyclin E and its inhibitor p21. The protein product of this cDNA, Ceb1, interacts with various cyclin subunits of CDKs in mammalian cells. Expression of Ceb1 is specifically detected in testis and ovary and is highly elevated when the functions of the tumor suppressor proteins, p53 and RB, are compromised by mutations or viral oncoproteins. The present results suggest that Ceb1 may play a critical role when its expression and the CDK activity are upregulated by inactivation of p53 and RB.

DOI： 10.1006/bbrc.1999.1777

Scopus

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical and Biophysical Research Communications  

p21(Cip1/Waf1) inhibits cell-cycle progression by binding to G1 cyclin/CDK complexes and proliferating cell nuclear antigen (PCNA) through its N- and C-terminal domains, respectively. Here, we report a novel p21(Cip1/Waf1)-interacting protein, Ciz1 (for Cip1 interacting zinc finger protein), which contains polyglutamine repeats and glutamine-rich region in the N-terminus as well as three zinc-finger motifs and one MH3 (matrin 3-homologous domain 3) in the C-terminal region, Ciz1 bound to the N-terminal, the CDK2-interacting part of p21(Cip1/Waf1), and the interaction was disrupted by the overexpression of CDK2. A region of about 150 amino acids containing the first zinc-finger motif in Ciz1 was the binding site for p21(Cip/Waf1). When Ciz1 and p21(Cip/Waf1) were individually overexpressed in U2-OS cells, they mostly localized in the nucleus. However, coexpression of Ciz1 induced cytoplasmic distribution of p21(Cip1/Waf1). These data indicate that Ciz1 is a unique nuclear protein that regulates the cellular localization of p21(Cip/Waf1).

DOI： 10.1006/bbrc.1999.1516

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FEBS Letters  

The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53. However, the function of MDMX has not been clarified yet. We found that MDM2 hetero-oligomerized with MDMX through their C-terminal RING finger domains. Yeast two-hybrid analysis revealed that the hetero-oligomerization between MDMX and MDM2 was more stable than the homo-oligomerization of each protein. MDM2 has been shown to be degraded by the ubiquitin-proteasome pathway, while MDMX was a stable protein. Interaction of MDMX with MDM2 through the C-terminal RING finger domains resulted in inhibiting degradation of MDM2. These data indicate that MDMX functions as a regulator of MDM2. Copyright (C) 1999 Federation of European Biochemical Societies.

DOI： 10.1016/S0014-5793(99)00254-9

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Leukemia  

We cloned a novel adaptor protein, APS (adaptor molecule containing Pleckstrin homology (PH) and Src Homology-2 (SH2) domains), which was tyrosine phosphorylated in response to c-kit or B cell receptor stimulation. Here, we report that APS was tyrosine phosphorylated by Janus kinase-2 (JAK2) at its C-terminal tyrosine residue and interacted with c-Cbl. Forced expression of APS in an erythropoietin (EPO)-dependent hematopoietic cell line resulted in reduced activation of STAT5 but not cell proliferation in response to EPO. APS bound to the phosphorylated tyrosine residue, Y343 of the erythropoietin receptor cytoplasmic domain. Co-expression of APS and c-Cbl, but not expression of either alone inhibited EPO-dependent STAT5 activation in 293 cells. This required the C-terminal phosphorylation site, as well as PH and SH2 domains of APS. Therefore, one of the major functions of APS is in recruitment of c-Cbl into the receptor/JAK complex, thereby inhibiting JAK signaling activity.

DOI： 10.1038/sj.leu.2401397

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochemical and Biophysical Research Communications  

We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.

DOI： 10.1006/bbrc.1997.7484

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature  

The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signaling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine- inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine- phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.

DOI： 10.1038/43213

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blood  

We searched for immediate early cytokine responsive genes and isolated a novel gene, CIS (Cytokine Inducible SH2 containing protein) that is induced in hematopoietic cells by a subset of cytokines including interleukin-2 (IL- 2), IL-3, and erythropoietin (EPO). The mutant IL-2 receptor that fails to activate STAT5 could not induce CIS, suggesting that STATS is involved in the cytokine-inducible expression of CIS. We cloned the 5'-flanking region of the CIS gene and found that about 200 bases upstream of the transcription- initiation site contain four potential STATS binding sites (MGF boxes). Luciferase reporter assays showed that these MGF boxes were essential for EPO-dependent promoter activity. Expression of STAT5 and the EPO receptor in HEK293 cells conferred EPO-dependent activation of the CIS promoter. These data indicate that CIS is a target of the JAK-STAT5 pathway of cytokine receptors. CIS contains an SH2 domain and binds to tyrosine-phosphorylated EPO and IL-3 receptors. In HEK293 cells expressing STAT5 and the EPO receptor, EPO-dependent tyrosine phosphorylation of STAT5, as well as EPO- dependent CIS-promoter activation, was suppressed when CIS was coexpressed. Moreover, the induction of oncostatin M, another STAT5 target, as well as the tyrosine-phosphorylation of STAT5, were partially suppressed by CIS expression in Ba/F3 cells. Thus, CIS is a feedback modulator of STAT5; its expression is induced by STAT5 and it negatively modulates STAT5 activation.

DOI： 10.1182/blood.v89.9.3148

Scopus

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：John Wiley & Sons  

DOI： 10.1111/j.1440-1835.1996.tb00037.x

開催年月日： 2017年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：長崎県長崎市  

開催年月日： 2017年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：宮城県仙台市  

開催年月日： 2017年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：宮城県仙台市  

開催年月日： 2016年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京都  

開催年月日： 2016年11月 - 2016年12月

記述言語：日本語   会議種別：ポスター発表  

開催地：神奈川県横浜市  

開催年月日： 2016年11月 - 2016年12月

記述言語：日本語   会議種別：ポスター発表  

開催地：神奈川県横浜市  

開催年月日： 2016年11月 - 2016年12月

記述言語：英語   会議種別：ポスター発表  

開催地：神奈川県横浜市  

開催年月日： 2016年8月

記述言語：英語   会議種別：ポスター発表  

開催地：Hong Kong  

開催年月日： 2016年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京  

開催年月日： 2016年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京  

開催年月日： 2016年6月

記述言語：英語   会議種別：ポスター発表  

開催地：San Francisco  

開催年月日： 2016年6月

記述言語：英語   会議種別：ポスター発表  

開催地：San Francisco  

開催年月日： 2016年5月

記述言語：英語   会議種別：ポスター発表  

開催地：Washington, DC  

開催年月日： 2016年3月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福島県郡山市  

開催年月日： 2016年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大阪  

開催年月日： 2016年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大阪  

開催年月日： 2015年10月

記述言語：英語   会議種別：ポスター発表  

開催地：愛知県名古屋市  

開催年月日： 2015年10月

記述言語：英語   会議種別：ポスター発表  

開催地：愛知県名古屋市  

　Incomplete abolition of tumorigenicity creates potential safety concerns in clinical trials of regenerative medicine based on human pluripotent stem cells (hPSCs). Previously, we demonstrated that survivin-responsive conditionally replicating adenoviruses regulated with multiple factors (Surv.m-CRAs), which selectively replicate in and kill a broad range of cancer-cell types, are promising anticancer agents. Here we examined the therapeutic potentials of m-CRAs against hPSCs. The survivin promoter was more active in undifferentiated hPSCs than the TERT promoter, whereas both promoters were minimally active in differentiated normal cells. Accordingly, Surv.m-CRA killed undifferentiated hPSCs more efficiently than Tert.m-CRAs; both m-CRAs exhibited efficient viral replication and cytotoxicity in hPSCs, but not in co-cultured differentiated normal cells. Pre-infection of hPSCs with m-CRA abolished in vivo teratoma formation in a dose-dependent manner following hPSC implantation into mice. Thus, m-CRAs, in particular Surv.m-CRAs, are potentially useful as both potent anticancer drugs and as novel antitumorigenic agents in hPSC-based regenerative medicine.

開催年月日： 2015年7月

記述言語：英語   会議種別：ポスター発表  

開催地：大阪  

開催年月日： 2015年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大阪  

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), are promising sources of material for use in cell transplantation therapy. However, the risk of formation of tumors, including teratomas and cancers originating from contaminating undifferentiated and transformed cells, represents the most critical obstacle to the safe clinical application of hPSC-based regenerative medicine. Multiple approaches have been taken to improve safety by reducing the risk of carcinogenesis. However, most previous studies focused on improving generation of hiPSCs by eliminating potential oncogenic factors, such as the oncogene c-myc, or by integrating the reprogramming transgenes into chromosomes. Although these sorts of strategies, classified here as the first safety approach, reduce the reprogramming-associated oncogenic potential of hiPSCs, they cannot completely eliminate tumorigenic potentials due to the intrinsic characteristics of hPSCs. We previously developed a novel method (adenoviral conditional targeting) that securely isolated target cells from other cell types and undifferentiated hPSCs (Mol Ther. 14(5): 673-683. 2006 ; Cover & News in the issue of the journal). This method, which can increase the efficacy and safety of hPSC-based regenerative medicine by decreasing tumorigenicity, is classified here as the second safety approach. Strategies that can directly target and kill, rather than merely inhibit, tumorigenic cells are classified here as the third safety approach (See Ide’s presentation). Conditionally replicating adenoviruses (CRAs), also called oncolytic adenoviruses, can selectively replicate in and kill cancer cells; consequently, CRAs represent attractive anticancer drugs. Previously, we developed a method for generating CRAs that can target cancers with multiple cancer-specific factors (m-CRAs); this approach further increased cancer specificity without reducing the anticancer effects. We also demonstrated that among candidate m-CRAs, survivin-responsive m-CRA (Surv.m-CRA) is one of the most promising anticancer agents, in two respects: superior cancer specificity (i.e., safety) and therapeutic efficacy relative to clinically tested telomerase reverse transcriptase (TERT)-responsive m-CRAs (Tert.m-CRAs), and strong anticancer effects against currently incurable cancer stem cells. Based on our careful and extensive preclinical studies, we have a plan to start the investigator initiated first-in-human clinical trial of Surv.m-CRA for malignant orthopedic tumors after J-IND approval, hopefully, this year (as presented in a preclinical symposium session). Here, we demonstrate that m-CRAs may also be useful as novel antitumorigenic agents in hPSC-based therapy. We show that the survivin promoter was more active in undifferentiated hPSCs than the TERT promoter, whereas both promoters were minimally active in differentiated normal cells. Accordingly, Surv.m-CRA killed undifferentiated hPSCs more efficiently than Tert.m-CRA; both m-CRAs exhibited efficient viral replication and cytotoxicity in undifferentiated hPSCs, but not in co-cultured differentiated normal cells. Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation in a dose- dependent manner following hPSC implantation into mice. Thus, we demonstrate that m-CRAs, in particular Surv.m-CRAs, are potentially useful as both potent anticancer drugs and as novel antitumorigenic agents in hPSC-based regenerative medicine; in the latter context, the viruses act by specifically killing contaminating undifferentiated hPSCs.

開催年月日： 2015年3月

記述言語：日本語  

開催地：神奈川  

国内学会

開催年月日： 2015年3月

記述言語：日本語  

開催地：神奈川  

国内学会

開催年月日： 2015年1月

記述言語：日本語  

開催地：鹿児島  

研究会

開催年月日： 2014年3月

記述言語：日本語  

開催地：京都  

国内学会

開催年月日： 2014年1月

記述言語：日本語  

開催地：鹿児島  

研究会

開催年月日： 2014年1月

記述言語：日本語  

開催地：鹿児島  

研究会

開催年月日： 2013年1月

記述言語：日本語  

開催地：鹿児島  

研究会

開催年月日： 2012年6月

記述言語：日本語  

開催地：熊本  

国内学会

開催年月日： 2012年6月

記述言語：日本語  

開催地：神奈川  

国内学会

開催年月日： 2012年6月

記述言語：日本語  

開催地：神奈川  

国内学会

開催年月日： 2012年6月

記述言語：日本語  

開催地：神奈川  

国内学会

開催年月日： 2012年1月

記述言語：日本語  

開催地：鹿児島  

研究会

開催年月日： 2010年12月

記述言語：日本語  

開催地：長崎  

国内学会

開催年月日： 2010年7月

記述言語：日本語  

開催地：栃木  

国内学会

開催年月日： 2010年3月

記述言語：日本語  

開催地：広島  

国内学会

開催年月日： 2010年3月

記述言語：英語  

開催地：福岡  

国際学会

記述言語：日本語   会議種別：ポスター発表  

対象： 高校生

種別：出前授業

「幹細胞と再生医学」についての講義