The Sirt1 deacetylase modulates the insulin-like growth factor signaling pathway in mammals
The Sirt1 deacetylase modulates the insulin-like growth factor signaling pathway in mammals
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DOI：
10.1016/j.mad.2005.04.006
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
McBurney, MW
中科院分区：
文献类型：
--
作者：
Lemieux, ME;Yang, X;McBurney, MW
线虫（秀丽隐杆线虫）的寿命可以通过影响胰岛素样生长因子（IGF）信号级联的组分的突变或通过过表达SIR2（一种NAD（+）依赖性蛋白脱乙酰酶）来延长。SIR2的哺乳动物同源物Sirt1已显示调节FoxO的活性，FoxO是IGF信号系统下游的转录因子。这些结果表明，Sirt1应该影响IGF途径。我们在这里报告的证据表明，这是小鼠的情况。小鼠中Sirt1蛋白的缺失导致IGF结合蛋白IGFBP I的表达增加，IGFBP I是IGF功能的分泌调节剂。Sirt1基因敲除小鼠的许多解剖学特征与过表达IGFBP1的转基因小鼠非常相似。我们的数据表明，Sirt.是限制IGFBP1产生从而调节IGF信号传导的调节环的一部分。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The lifespan of the nematode, Caenorhabditis elegans, can be extended by mutations affecting components of the insulin-like growth factor (IGF) signaling cascade or by overexpression of SIR2, an NAD(+)-dependent protein deacetylase. The mammalian homologue of SIR2, Sirt1, has been shown to modulate the activity of FoxO, a transcription factor that is downstream of the IGF signaling system. These results suggest that Sirt1 ought to affect the IGF pathway. We report here evidence that this is the case in mice. The loss of Sirt1 protein in mice results in increased expression of the IGF binding protein IGFBP I, a secreted modulator of IGF function. A number of the anatomical characteristics of Sirt1-null mice closely resemble those of transgenic mice overexpressing IGFBP1. Our data suggest that Sirt. is part of a regulatory loop that limits the production of IGFBP1 thereby modulating IGF signaling. (c) 2005 Elsevier Ireland Ltd. All rights reserved.