The transcription activity of heat shock factor 4b is regulated by FGF2.

The transcription activity of heat shock factor 4b is regulated by FGF2.
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热休克因子 4b 的转录活性受 FGF2 调节。

DOI:
10.1016/j.biocel.2012.11.013
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发表时间:
2013-02
期刊:
Int J Biochem Cell Biol
影响因子:
--
通讯作者:
胡延忠
胡延忠
中科院分区:
其他
文献类型:
--
作者:
胡延忠

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热休克因子4 b与出生后透镜的发育密切相关。它在出生后的透镜上皮细胞和次级纤维细胞中表达,并控制对透镜内环境稳定重要的小热休克蛋白的表达。然而,Hsf 4 b的信号通路仍然没有完全理解。在这里,我们提出,Hsf 4 b转录活性的调节FGF 2的一个关键的生长因子,参与调节透镜发展的多个阶段。FGF 2可以促进Hsf 4 b核转位和Hsp 25和α B-晶状体蛋白的表达,这是Hsf 4 b重建的小鼠hsf 4 −/−透镜上皮细胞中Hsf 4 b的关键下游靶点。进一步的研究表明,FGF 2可以通过ERK 1/2介导的翻译后磷酸化或类小泛素化来诱导Hsf 4 b蛋白的稳定。Hsf 4 b可促进FGF 2诱导的透镜上皮细胞向纤维细胞的形态转变,ERK 1/2抑制剂U 0126可抑制这种形态转变。综上所述,我们的数据表明,Hsf 4 b是一种新的下游转录因子的FGF 2,其转录活性与FGF 2调节的透镜上皮细胞-纤维细胞转换。
Heat shock factor 4b has been found to be closely associated with postnatal lens development. It expresses in postnatal lens epithelial and secondary fiber cells and controls the expression of small heat shock proteins which are important for lens homeostasis. However, the signal pathways underlying Hsf4b are still not completely understood. Here we present that Hsf4b transcription activity is regulated by FGF2 a key growth factor that is involved in regulating lens development at multiple stages. FGF2 can promote Hsf4b nuclear-translocation and the expression of Hsp25 and αB-crystallin, the key downstream targets of Hsf4b in the Hsf4b-reconstituted mouse hsf4−/− lens epithelial cells. Further study indicates that FGF2 can induce Hsf4b protein stabilization through ERK1/2-mediated posttranslational phosphorylation or sumoylation. Hsf4b can promote FGF2-induced morphology transition from lens epithelial cell to the fiber cell, and this morphology transition can be inhibited by ERK1/2 inhibitor U0126. Taken together, our data demonstrate that Hsf4b is a novel downstream transcription factor of FGF2, and its transcription activity is associated with FGF2-modulated lens epithelial cell–fiber cell transition.
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