70 kDa热休克蛋白介导功能性核因子-κB的核内靶向递送
Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein.
作者信息
Fujihara S M, Nadler S G
机构信息
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543, USA.
出版信息
EMBO J. 1999 Jan 15;18(2):411-9. doi: 10.1093/emboj/18.2.411.
Abstract
The 70 kDa heat shock protein (Hsp70) is a highly conserved, ubiquitous protein involved in chaperoning proteins to various cellular organelles. Here we show that when added exogenously to cells, Hsp70 is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion. We exploited this ability of Hsp70 to deliver NF-kappaB, a key transcriptional regulator of inflammatory responses. We demonstrate that a fusion protein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kappaB was directed into the nucleus of cells, could bind DNA specifically, and activated Igkappa expression and TNFalpha production. We therefore propose that Hsp70 can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses.
摘要
70千道尔顿热休克蛋白（Hsp70）是一种高度保守、广泛存在的蛋白质，参与将蛋白质伴侣运输到各种细胞器。我们在此表明，当外源添加到细胞中时，Hsp70以细胞类型特异性方式很容易导入细胞质和细胞核区室。我们利用Hsp70的这种能力来递送核因子κB（NF-κB），它是炎症反应的关键转录调节因子。我们证明，由C端Hsp70肽和NF-κB的p50亚基组成的融合蛋白被导向细胞的细胞核，能够特异性结合DNA，并激活免疫球蛋白κ轻链（Igκ）表达和肿瘤坏死因子α（TNFα）产生。因此，我们提出Hsp70可作为蛋白质或DNA胞质内和核内递送的载体，以调节基因表达，从而控制免疫反应。
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