noxin, a novel stress-induced gene involved in cell cycle and apoptosis
noxin, a novel stress-induced gene involved in cell cycle and apoptosis
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DOI：
10.1128/mcb.00551-06
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发表时间：
2007-08-01
影响因子：
5.3
通讯作者：
Enikolopov, Grigori
中科院分区：
文献类型：
--
作者：
Nakaya, Naoki;Hemish, Jill;Enikolopov, Grigori
我们描述了一种新的应激诱导基因，noxin，和一个敲除小鼠线与失活的noxin基因。noxin基因在基因组中没有sequelog，编码一种富含丝氨酸的蛋白质，具有ATM、Akt和DNA依赖性蛋白激酶激酶的预测磷酸化位点;核定位信号;和锌指结构域。noxin mRNA和蛋白质水平受细胞周期的严格控制。被鉴定为一氧化氮诱导基因的noxin被广泛的应激信号强烈诱导：γ-和UV照射、过氧化氢、阿霉素和细胞因子。这种诱导依赖于p53。Noxin在细胞核中积累以响应应激，并且当异位表达时，Noxin将细胞周期阻滞在G（1）;虽然它也诱导p53，但Noxin的细胞周期阻滞功能不依赖于p53活性。noxin基因敲除小鼠是存活的和可生育的;然而，它们具有增大的心脏、几个改变的造血参数和减少的精子细胞数量。重要的是，Noxin的丢失或下调导致细胞死亡增加。我们的研究结果表明，Noxin可能是细胞防御系统的一个组成部分：它被各种应激刺激激活，帮助细胞退出周期，并对抗凋亡。
We describe a novel stress-induced gene, noxin, and a knockout mouse line with an inactivated noxin gene. The noxin gene does not have sequelogs in the genome and encodes a highly serine-rich protein with predicted phosphorylation sites for ATM, Akt, and DNA-dependent protein kinase kinases; nuclear localization signals; and a Zn finger domain. noxin mRNA and protein levels are under tight control by the cell cycle. noxin, identified as a nitric oxide-inducible gene, is strongly induced by a wide range of stress signals: gamma- and UV irradiation, hydrogen peroxide, adriamycin, and cytokines. This induction is dependent on p53. Noxin accumulates in the nucleus in response to stress and, when ectopically expressed, Noxin arrests the cell cycle at G(1); although it also induces p53, the cell cycle arrest function of Noxin is independent of p53 activity. noxin knockout mice are viable and fertile; however, they have an enlarged heart, several altered hematopoietic parameters, and a decreased number of spermatids. Importantly, loss or downregulation of Noxin leads to increased cell death. Our results suggest that Noxin may be a component of the cell defense system: it is activated by various stress stimuli, helps cells to withdraw from cycling, and opposes apoptosis.