Hzf regulates adipogenesis through translational control of C/EBPα

Hzf regulates adipogenesis through translational control of C/EBPα
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DOI:
10.1038/emboj.2008.76
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发表时间:
2008-05-21
期刊:
影响因子:
11.4
通讯作者:
Sugimoto, Masataka
Sugimoto, Masataka
中科院分区:
生物学1区
文献类型:
--
作者:
Kawagishi, Hiroyuki;Wakoh, Takeshi;Sugimoto, Masataka

文献摘要

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脂肪细胞分化需要一个明确的基因表达程序,其中转录因子C/EBP α (CCAAT/增强子结合蛋白)具有核心功能。在这里,我们发现Hzf(造血锌指),一个先前确定的p53转录靶点,调节C/EBP α的表达。Hzf在前脂肪细胞系分化过程中被诱导,短发夹RNA对其抑制会破坏脂肪形成。在Hzf缺失的情况下,由于C/EBP α mRNA的翻译减少,其表达严重受损。Hzf与C/EBP α mRNA的3'非翻译区相互作用以增强其翻译。综上所述,这些发现强调了Hzf在脂肪形成调控级联中的关键作用。
Adipocyte differentiation requires a well-defined programme of gene expression in which the transcription factor C/EBP alpha (CCAAT/enhancer-binding protein) has a central function. Here, we show that Hzf (haematopoietic zinc-finger), a previously identified p53 transcriptional target, regulates C/EBP alpha expression. Hzf is induced during differentiation of preadipocyte cell lines, and its suppression by short hairpin RNA disrupts adipogenesis. In Hzf's absence, expression of C/EBP alpha is severely impaired because of reduced translation of its mRNA. Hzf physically interacts with the 3' untranslated region of C/EBP alpha mRNA to enhance its translation. Taken together, these findings underscore a critical role of Hzf in the adipogenesis regulatory cascade.