Analysis on the mechanism of survival, growth and differentiation of hematopoietic cells

造血细胞存活、生长和分化机制分析

基本信息

批准号：
14370302
负责人：
KANAKURA Yuzuru
金额：
$ 9.6万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370302/
关键词：
KIT FLT3 ROS E2F1 NF-kB apoptosis Anamorsin Bcl-XL NF-κB PML 増殖分化シグナル伝達 STAT3 転写因子白血病 RARα

项目摘要

In this study, we have analyzed the mechanisms of growth, differentiation and malignant transformation of hematopoietic cells from the aspects of signal transduction, transcriptional regulation, cell cycle regulation and apoptosis and got the results as follows :1.Both wild-type KIT and oncogenic (Asp814Val) KIT induce cell growth by activating PI3-K signal pathway through Tyrosine719.2.Wild type KIT mediates chemotaxis by activating Src family tyrosine kinases and PI3-K through Tyrosine719 and Tyrosine567.3.Oncogenic FLT3 containing the internal tandem duplication (ITD) enhances the expression of Pim-2 that mediates cell growth, while it suppresses that of PU.1 and c/EBPa, both of which induce granulocytic differentiation, thereby enhancing the growth and inhibiting the differentiation of immature myeloid cells.4.Functional cooperation among Ras, STAT5, and PI3-K is required for full oncogenic activity of BCR/ABL oncogene.5.PML inhibits STAT3 activity, while its oncogenic form PML/RARa enhances its activity.6.E2F1, a critical regulator of Gl/S transition, sensitizes host cells to apoptosis by inhibiting NF-kB activity specifically at Gl/S transition.7.We have cloned a novel anti-apoptotic molecule Anamorsin, which reveals no homology to known apoptosis related molecules.8.Knockout mice for Anamorsin are embryonic lethal at late gestation due to the defect of definitive hematopoiesis.

在这项研究中，我们分析了造血细胞的生长，分化和恶性转化的机制，从信号转导，转录调控，细胞周期调节和凋亡方面的各个方面，结果如下：1。1.1.均为野生型KIT和ONCINIC-ONCENIC-ONCENIC 7通过tyrige-tyr-tyr-tyr-tyr-tyrigntyr.tryn9。 KIT通过激活SRC家族酪氨酸激酶和PI3-K通过酪氨酸719和酪氨酸567.3.-结合内部串联复制（ITD）增强PIM-2的表达，从而介导PU.1和C/C/C/C/C/C/C/C/C/C/C/C/C/C/C/eBPA的表达，从而介导了趋化性。 inhibiting the differentiation of immature myeloid cells.4.Functional cooperation among Ras, STAT5, and PI3-K is required for full oncogenic activity of BCR/ABL oncogene.5.PML inhibits STAT3 activity, while its oncogenic form PML/RARa enhances its activity.6.E2F1, a critical regulator of Gl/S transition, sensitizes host cells to apoptosis by inhibiting 7.我们已经克隆了一种新型的抗凋亡分子异糖素的NF-KB活性。7。Anamorsin的Nockout小鼠在妊娠后期因妊娠而导致的胚胎致死性，该抗凋亡分子异霉素与已知凋亡相关的分子没有同源性。