研究c-Jun的調控與細胞命運的關係

The relationship between c-Jun regulation and cell fates

劉若娟(Juo Chung Liu)

指導教授 ： 黃惠美

臺北醫學大學/醫學院/細胞及分子生物研究所/碩士(2005年)

摘要

轉錄因子c-Jun在細胞增生，存活和分化上皆扮演重要的角色。據最近的文獻指出，在人類造血前驅細胞中，c-Jun會抑制EPO及SCF所誘導的紅血球系分化。而c-Jun在其它細胞激素及化學試劑誘導的紅血球系分化過程中所扮演的角色未明。因此，在本篇論文中，我們發現細胞激素( activinA及TGF-?)及hemin，Bcr/Abl 抑制劑STI571會抑制human erythroid leukemia cell line K562細胞的c-Jun表現量。但HDACIs (apicidine，sodium butyrate，MS275)並不抑制c-Jun的表現。經由c-Jun大量表現的分析，發現c-Jun不影響細胞增生，但抑制STI571，TGF-?，Hemin，HDACIs所誘導的分化。此外，c-Jun可回復activinA所抑制的細胞增生，且抑制activinA所誘導的血紅素合成。Activin A活化的p38 pathway 受到抑制時，則 c-Jun蛋白表現會增加。這些結果顯示，activin A可透過p38 pathway 負調控c-Jun使紅血球系分化。

關鍵字

分化調控

並列摘要

The transcription factor c-Jun plays important roles in cell proliferation, survival, and differentiation. It has been demonstrated recently that c-Jun inhibits EPO and SCF-mediated erythroid differentiation in primary human hematopoietic progenitors. However, the role of c-Jun in other cytokines and chemical agents-mediated erythroid differentiation is unknown. In this study, we found that cytokines (activinA and TGF-?), hemin, and Bcr/Abl inhibitator STI571 down-regulated c-Jun expression in hematopoietic progenitor cell line K562, but histone deacetylase inhibitators (HDACIs : apicidine, sodium butyrate, MS271) did not . We examined the effect of c-Jun overexpression in K562 cells. Stable clones overexpressing c-Jun showed no alterations in proliferation but blocked TGF-???hemin and HDACIs -mediated hemoglobin synthesis. In addition, c-Jun restored activin A-inhibited proliferation and blocked activinA-induced hemoglobin synthesis. The blocking of activin A -mediated p38 MAPK activation that up-regulated c-Jun expression. These data suggest that activin A down-regulated c-Jun via p38 MAPK pathway to mediate erythroid differentiation.

並列關鍵字

differentiation ； c-Jun

參考文獻

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