Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5
Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5
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DOI：
10.1016/j.yexcr.2008.05.008
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Hiroaki, Hidekazu
中科院分区：
文献类型：
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作者：
Goda, Natsuko;Tenno, Takeshi;Hiroaki, Hidekazu
胰岛素样生长因子结合蛋白（IGFBPs）具有多种胰岛素样生长因子非依赖性细胞活性，包括受体非依赖性细胞摄取和转录调控，但细胞进入机制尚不清楚。在这里，我们集中在他们的受体独立的细胞进入机制的蛋白转导结构域（PTD）的活动，这是一个新兴的技术，可用于临床应用。来自IGFBP-3和IGFBP-5的18个氨基酸残基的肽，其涉及肝素结合区，介导外源蛋白质向NIH 3 T3和HeLa细胞的细胞递送。IGFBP-3/5衍生肽的相对蛋白质递送活性与HIV-Tat肽（一种有效的PTD）的相对蛋白质递送活性相比约为20-150%。肝素抑制IGFBP-3和IGFBP-5的融合蛋白的摄取，表明递送途径是肝素依赖性内吞作用，类似于HIV-Tat。融合到HIV-Tat的GST的递送被IGFBP-3或IGFBP-5衍生的合成肽竞争。因此，三种PTD的进入途径是共享的。我们的数据显示了一种基于IGFBP-3/5衍生肽的IGF非依赖性活性的分子机制设计蛋白质递送系统的新方法。(c)2008年爱思唯尔公司All rights reserved.
Insulin-like growth factor binding proteins (IGFBPs) have various IGF-independent cellular activities, including receptor-independent cellular uptake followed by transcriptional regulation, although mechanisms of cellular entry remain unclear. Herein, we focused on their receptor-independent cellular entry mechanism in terms of protein transduction domain (PTD) activity, which is an emerging technique useful for clinical applications. The peptides of 18 amino acid residues derived from IGFBP-3 and IGFBP-5, which involve heparin-binding regions, mediated cellular delivery of an exogenous protein into NIH3T3 and HeLa cells. Relative protein delivery activities of IGFBP-3/5-derived peptides were approximately 20-150% compared to that of the HIV-Tat peptide, a potent PTD. Heparin inhibited the uptake of the fusion proteins with IGFBP-3 and IGFBP-5, indicating that the delivery pathway is heparin-dependent endocytosis, similar to that of HIV-Tat. The delivery of GST fused to HIV-Tat was competed by either IGFBP-3 or IGFBP-5-derived synthetic peptides. Therefore, the entry pathways of the three PTDs are shared. our data has shown a new approach for designing protein delivery systems using IGFBP-3/5 derived peptides based on the molecular mechanisms of IGF-independent activities of IGFBPs. (c) 2008 Elsevier Inc. All rights reserved.