Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis

Naofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis
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DOI:
10.1016/j.bbrc.2010.02.133
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发表时间:
2010-03-26
影响因子:
3.1
通讯作者:
Ishikawa, Naohisa
Ishikawa, Naohisa
中科院分区:
生物学4区
文献类型:
--
作者:
Feng, Guo-Gang;Li, Chang;Ishikawa, Naohisa

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最近从大鼠脑/脊髓cDNA文库中鉴定出Naofen作为抗志贺毒素(Stx)-2抗体的反应性物质。脑芬mRNA由4620个核苷酸组成,编码1170个氨基酸。Naofen在其N-末端含有四个WD-重复结构域,并且广泛分布于大鼠的许多组织中。肿瘤坏死因子(TNF)-α以剂量依赖方式增强HEK 293细胞中naofen mRNA的表达。此外,naofen siRNA,主要敲低naofen mRNA的表达,显着降低TNF-α诱导的caspase-3激活和凋亡的HEK 293细胞。在HEK 293细胞(FLAG-NF)中过表达naofen可自发诱导caspase-3激活和凋亡,并对TNF-α诱导的凋亡表现出极高的敏感性。这些结果表明,脑芬可能作为一种新的调节剂激活caspase-3,并促进TNF-α刺激的细胞凋亡。(C)2010年爱思唯尔公司All rights reserved.
Naofen has recently been identified from the rat brain/spinal cord cDNA library as a substance reactive against an anti-shigatoxin (Stx)-2 antibody. Naofen mRNA is composed of 4620 nucleotides and encodes 1170 amino acids. Naofen contains four WD-repeat domains in its N-terminus and is ubiquitously distributed in many tissues of the rat. Tumor necrosis factor (TNF)-alpha enhanced the expression of naofen mRNA in HEK293 cells in a dose-dependent manner. Furthermore, naofen siRNA, which predominantly knocked down the expression of naofen mRNA, significantly reduced both TNF-alpha-induced caspase-3 activation and apoptosis in HEK293 cells. Overexpression of naofen in HEK293 cells (FLAG-NF) spontaneously induced caspase-3 activation and apoptosis, and showed extremely high susceptibility to TNF-alpha-induced apoptosis. These results indicated that naofen may function as a novel modulator activating caspase-3, and promoting TNF-alpha-stimulated apoptosis. (C) 2010 Elsevier Inc. All rights reserved.