Development of novel anti-tumor drugs inhibiting Anamorsin and Picot binding

开发抑制Anamorsin和Picot结合的新型抗肿瘤药物

• 批准号: 23591387
• 负责人: SAITOH Norimitsu
• 金额: $ 3.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591387/
• 关键词: Anamorsin; Picot; 鉄硫黄クラスター; 細胞内シグナル伝達; Ras; Bリンパ球; LPS; B細胞性リンパ腫; PICOT; 鉄・硫黄クラスター; トランスジェニック; ERK1/2; IkB; P53; PKC; P38MAPK

Anamorsin (AM) was originally isolated as a molecule that conferred resistance to apoptosis. AM deficient mice die during late gestation; AM is indispensable for embryo growth and hematopoiesis. Furthermore, our previous study showed AM overexpression in approximately 30% of B cell neoplasm cases. In this work, we focused on B cells of AM transgenic (Tg) mice. LPS-stimulated proliferation of AM Tg B cells was decreased compared with WT mice. Phosphorylation of Erk1/2 and IKBa in LPS-stimulated AM Tg B cells was also decreased. Upstream analysis based on the results of DNA micro array comparing AM Tg and WT B cells stimulated with or without LPS suggested that Ras activation was decreased in LPS-stimulated AM Tg B cells. We also confirmed impairment of LPS induced Ras activation in AM Tg mice by Ras assay. Our findings indicate the possibility that AM plays a role of negative regulation in LPS signaling pathway through the inhibition of Ras activation, which is a novel function of AM.

Anamorsin（AM）最初是作为一种赋予细胞凋亡抗性的分子分离的。AM缺陷小鼠在妊娠晚期死亡; AM是胚胎生长和造血不可缺少的。此外，我们先前的研究显示AM过表达在大约30%的B细胞肿瘤病例中。本研究以AM转基因（Tg）小鼠的B细胞为研究对象。与WT小鼠相比，LPS刺激的AM Tg B细胞增殖减少。LPS刺激的AM Tg B细胞中Erk 1/2和IKBa的磷酸化也降低。基于DNA微阵列结果的上游分析比较了用或不用LPS刺激的AM Tg和WT B细胞，表明在LPS刺激的AM Tg B细胞中Ras活化降低。我们还通过Ras测定证实了LPS诱导的AM Tg小鼠Ras活化的损伤。我们的研究结果表明，AM可能通过抑制Ras活化而对LPS信号通路起负调节作用，这是AM的一种新功能。

项目成果

MS4A3発現はヒト造血における早期骨髄球系分化の指標となる

MS4A3表达是人类造血早期骨髓分化的指标

• 发表时间: 2013
• 作者: Yamauchi T;Takenaka ,以下12名;保仙直毅;石橋知彦,横田貴史,柴山浩彦,織谷健司,金倉譲ほか
• 通讯作者: 石橋知彦,横田貴史,柴山浩彦,織谷健司,金倉譲ほか

An anti-apoptotic molecule, Anamorsin, is essential for erythropoiesis through the regulation of cellular labile iron pool The American Society of Hematology

抗凋亡分子阿纳莫辛通过调节细胞不稳定铁库对红细胞生成至关重要 美国血液学会

• 发表时间: 2012
• 作者: Tanimura A;Hamanaka Y;Saitoh N;Oritani K;Shibayama H;Kanakura Y et al
• 通讯作者: Kanakura Y et al

Autoimune Cytopenia合併が考えられた慢性リンパ性白血病の1例

慢性淋巴细胞白血病合并自身免疫性血细胞减少症一例

• 发表时间: 2011
• 作者: Ayuko Taniguchi;Yumiko Hashida;Yuiko Nemoto;Takahiro Taguchi;Yoshito Iwahara;Masanori Daibata.;西嶌悠,齊藤則充,織谷健司,金倉譲ほか
• 通讯作者: 西嶌悠,齊藤則充,織谷健司,金倉譲ほか

Identification of osteoblast stimulating factor-5 as a novel regulator of early lymphocyte development.

鉴定成骨细胞刺激因子 5 作为早期淋巴细胞发育的新型调节剂。

• 发表时间: 2012
• 作者: Fujita N;et al
• 通讯作者: et al

Significance of novel HSC marker ESAM expression in cord blood

脐带血中新型 HSC 标志物 ESAM 表达的意义

• 作者: Fresquet V;et al.;T Ishibashi
• 通讯作者: T Ishibashi