| Summary: | 碩士 === 臺北醫學大學 === 細胞及分子生物研究所 === 93 === 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.
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