Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death.

Induction of Id-1 by FGF-2 involves activity of EGR-1 and sensitizes neuroblastoma cells to cell death.
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DOI:
10.1002/jcp.22505
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发表时间:
2011-07
影响因子:
5.6
通讯作者:
Peruzzi, Francesca
Peruzzi, Francesca
中科院分区:
生物学2区
文献类型:
--
作者:
Passiatore, Giovanni;Gentilella, Antonio;Rom, Slava;Pacifici, Marco;Bergonzini, Valeria;Peruzzi, Francesca

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分化抑制因子-1(Inhibitor of differentiation-1,Id-1)是螺旋-环-螺旋(helix-loop-helix,HLH)蛋白家族的一员,通过与碱性HLH转录因子的抑制性结合来调节基因转录。与该家族的其他成员类似,Id-1参与细胞分化的抑制和细胞生长的激活。Id-1的双重功能,即抑制分化和刺激细胞增殖,可能是相互依赖的,因为细胞分化通常与退出细胞周期相关联。成纤维细胞生长因子-2(FGF-2)在中枢神经系统(CNS)发育过程中的不同生物学过程中发挥着多种作用。此外,FGF-2已被描述为诱导神经母细胞瘤SK-N-MC细胞中的“神经元样”分化并触发细胞凋亡。虽然几种促有丝分裂因子对Id-1蛋白的调节是公认的,但对FGF-2在Id-1调节中的作用知之甚少。使用人神经母细胞瘤细胞系SK-N-MC,我们发现,这些细胞与FGF-2的治疗导致早期诱导Id-1 mRNA和蛋白。诱导发生在FGF-2处理后1小时内,并由ERK 1/2途径介导,ERK 1/2途径反过来刺激早期生长反应-1(Egr-1)转录因子的表达。我们还证明了Egr-1与Id-1启动子在体外和细胞培养中的直接相互作用。最后,Id-1表达的抑制导致FGF-2处理的细胞的G2/M积累和延迟的细胞死亡。
Inhibitor of differentiation-1 (Id-1) is a member of helix–loop–helix (HLH) family of proteins that regulate gene transcription through their inhibitory binding to basic-HLH transcription factors. Similarly to other members of this family, Id-1 is involved in the repression of cell differentiation and activation of cell growth. The dual function of Id-1, inhibition of differentiation, and stimulation of cell proliferation, might be interdependent, as cell differentiation is generally coupled with the exit from the cell cycle. Fibroblast growth factor-2 (FGF-2) has been reported to play multiple roles in different biological processes during development of the central nervous system (CNS). In addition, FGF-2 has been described to induce “neuronal-like” differentiation and trigger apoptosis in neuroblastoma SK-N-MC cells. Although regulation of Id-1 protein by several mitogenic factors is well-established, little is known about the role of FGF-2 in the regulation of Id-1. Using human neuroblastoma cell line, SK-N-MC, we found that treatment of these cells with FGF-2 resulted in early induction of both Id-1 mRNA and protein. The induction occurs within 1 h from FGF-2 treatment and is mediated by ERK1/2 pathway, which in turn stimulates expression of the early growth response-1 (Egr-1) transcription factor. We also demonstrate direct interaction of Egr-1 with Id-1 promoter in vitro and in cell culture. Finally, inhibition of Id-1 expression results in G2/M accumulation of FGF-2-treated cells and delayed cell death.
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