Studies on intracellular factors involved in cellular differentiation of mouse and human cells.

参与小鼠和人类细胞分化的细胞内因子的研究。

• 批准号: 63480509
• 负责人: OISHI Michio
• 金额: $ 4.48万
• 依托单位: Inst. of Applied Microbiol. University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480509/
• 关键词: Differentiation; Embryonal; Phosphorylation; erythroid; 分化; DIF-III; herbimycin A; genistein; ST 638; DIF-I; DIF-II; 分化決定因子(commitment factor)

We have found that herbimycin A is an effective inducing agent capable of triggering differentiation in two typical mouse in vitro differentiation systems, which have been considered to be quite different in their mechanism of induction: endoderm differentiation of embryonal carcinoma (F9) cells and terminal erythroid differentiation of (MEL) cells. The results suggest that there is a common step in the intracellular differentiation cascade which is, directly or indirectly, associated with phosphorylation at specific (tyrosine) residues of cellular proteins.An erythroid-inducing activity was detected in cell-free extracts from MEL cells which had been incubated with dimethyl sulfoxide or hexamehylenebisacetamide for a prolonged period of time. The newly detected activity was apparently different from the previously reported differentiation-inducing factors and seemed to be derived from a proeinacious factor in the cytoplasm. The timing of the appearance of the activity in the extracts coincided with that of cellular commitment to differentiation. The activity was not induced in a differentiation defective MEL cell line and the induction of the activity was inhabited by PMA, a specific inhibitor for MEL cell differentiation.

我们发现除莠霉素A是一种有效的诱导剂，能够在两种典型的小鼠体外分化系统中触发分化，这两种分化系统被认为在其诱导机制上是完全不同的：胚胎癌细胞（F9）的内胚层分化和（MEL）细胞的终末红系分化。结果表明，有一个共同的步骤，在细胞内分化级联这是，直接或间接地，与磷酸化在特定的（酪氨酸）残基的细胞protein.A红细胞诱导活性检测无细胞提取物从MEL细胞已与二甲基亚砜或六亚甲基双乙酰胺孵育一段较长的时间。新检测到的活性明显不同于以前报道的分化诱导因子，似乎来自细胞质中的proeinacious因子。在提取物中的活性的外观的时间与细胞分化的承诺。该活性在分化缺陷MEL细胞系中不被诱导，并且该活性的诱导被MEL细胞分化的特异性抑制剂PMA抑制。

项目成果

Kaneko-Ishino, T., T.U. Kume, H. Sasaki, M. Obinata and M. Oishi.: "Effect of c-myc gene expression on the early inducible reactions required for erythroid differentiation in vitro." Mol. Cell. Biol., 8, 5545-5548, 1988.

金子石野，T.，T.U.

Watanabe,T.;S.Nomura;T.Kaneko;S.Yamagoe;T.Kamiya;M.Oishi: The status of differentiation thrapy of cancer (Raven press). 45. 215-228 (1988)

Watanabe，T.；S.Nomura；T.Kaneko；S.Yamagoe；T.Kamiya；M.Oishi：癌症分化治疗的现状（Raven press）。

Watanabe,T.,T.Shiraishi,H.Sasaki and M.Oishi: "Inhibitors for protein-tyrosine kinase,ST638 and genistein,induce differentiation of mouse erythroleukemia cellos in a synergistic manner." Exp.Cell Res.183. 335-342 (1989)

Watanabe,T.,T.Shiraishi,H.Sasaki 和 M.Oishi：“蛋白酪氨酸激酶抑制剂、ST638 和金雀异黄素，以协同方式诱导小鼠红白血病细胞分化。”

Watanabe,T.,S.Nomura,T.Kaneko,S.Yamagoe and M.Oishi: "Intracellular factors involved in erythroid differentiation of mouse erythroleukemia cellos." In “The status of differentiation therapy"Raven Press. 45. 215-228 (1988)

Watanabe, T., S. Nomura, T. Kaneko, S. Yamagoe 和 M. Oishi：“细胞内因子参与小鼠红白血病细胞的红细胞分化。”《分化治疗的现状》，Raven Press，45。 -228 (1988)

Watanabe, T., T. Shiraishi, H. Sasaki and M. Oishi.: "Inhibitors for protein-tyrosine kinase, ST638 and genistein, induce differentiation of mouse erythroleukemia cells in a synergistic manner." Exp. Cell Res., 183, 335-342, 1989.

Watanabe, T.、T. Shiraishi、H. Sasaki 和 M. Oishi.：“蛋白酪氨酸激酶抑制剂 ST638 和金雀异黄素以协同方式诱导小鼠红白血病细胞分化。”