p38β, A novel regulatory target of Pokemon in hepatic cells.

p38β, A novel regulatory target of Pokemon in hepatic cells.
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p38β,肝细胞中神奇宝贝的新调控目标

DOI:
10.3390/ijms140713511
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发表时间:
2013-06-27
影响因子:
5.6
通讯作者:
Jiang Y
Jiang Y
中科院分区:
生物学2区
文献类型:
--
作者:
Chen Z;Liu F;Zhang N;Cao D;Liu M;Tan Y;Jiang Y

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Pokemon是一种重要的原癌基因,参与细胞分化、肿瘤发生和转移等多种生物过程和癌症发展。 Pokemon 被认为是位于几个癌基因上游的转录因子,调节它们的表达。 p38MAPK 在与炎症反应、细胞增殖、分化和存活相关的细胞信号传导通路中充当关键调节因子。 p38β是p38MAPK家族的成员,与肿瘤发生密切相关,但其激活机制尚不清楚。在这项研究中,我们发现Pokemon的过度表达促进了HepG2细胞的生长、迁移和侵袭。然而,p38抑制剂SB202190有效减弱了Pokemon对HepG2细胞的促进作用。 Pokemon 的靶向表达或沉默改变了细胞 p38β 蛋白水平和 p38 信号通路中下游 ATF2 的磷酸化。双荧光素酶报告分析和 ChIP 分析均表明 p38β 是转录因子 Pokemon 的新调控靶点,并在肝细胞中受到 Pokemon 的正向调控。
Pokemon is an important proto-oncogene involved in various biological processes and cancer development, such as cell differentiation, tumorigenesis and metastasis. Pokemon is recognized as a transcription factor localized upstream of several oncogenes, regulating their expression. p38MAPKs act as key regulatory factors in cellular signaling pathways associated with inflammatory responses, cell proliferation, differentiation and survival. p38β, a member of p38MAPK family, is closely correlated with tumorigenesis, but the mechanism of activation remains unclear. In this study, we found overexpression of Pokemon promoted the growth, migration and invasion of HepG2 cells. However, a p38 inhibitor SB202190 efficiently attenuated the promoting effect of Pokemon in the HepG2 cells. Targeted expression or silencing of Pokemon changed cellular p38β protein level and phosphorylation of downstream ATF2 in the p38 signaling pathway. Both dual luciferase report assay and ChIP assay suggested that p38β is a novel regulatory target of the transcription factor Pokemon and positively regulated by Pokemon in hepatic cells.
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