A protective strategy against hyperinflammatory responses requiring the nontranscriptional actions of GPS2.
A protective strategy against hyperinflammatory responses requiring the nontranscriptional actions of GPS2.
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DOI：
10.1016/j.molcel.2012.01.025
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发表时间：
2012-04-13
期刊：
影响因子：
16
通讯作者：
Perissi, Valentina
中科院分区：
文献类型：
--
作者：
Cardamone, M. Dafne;Krones, Anna;Tanasa, Bogdan;Taylor, Havilah;Ricci, Laura;Ohgi, Kenneth A.;Glass, Christopher K.;Rosenfeld, Michael G.;Perissi, Valentina
高度炎症状态和许多疾病之间的关联被广泛认可，但我们对已经发展以防止炎症反应的不受控制的激活的分子策略的理解仍然不完整。在这里，我们报告了一个关键的，非转录的作用，GPS 2作为一个监护人对过度刺激的TNFα诱导的基因程序。GPS 2细胞质作用是通过抑制TRAF 2/Ubc 13酶活性来特异性调节RIP 1泛素化和JNK活化所必需的。通过抑制巨噬细胞中的TNFα靶基因和通过改善aP 2-GPS 2转基因小鼠脂肪组织中的胰岛素信号传导，证实了GPS 2抗炎作用的体内相关性。由于非转录作用由GPS 2作为核受体的正性和负性辅因子发挥作用来补充，因此体内过表达也导致抵抗素的循环水平升高和肝脂肪变性的发展。总之，这些研究将GPS 2定义为精确控制参与免疫和稳态的炎症反应所需的分子监护人。
The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of the TNFα-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFα target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of Resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis.
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影响因子：
12.3
作者：
Kircher M;Stenzel U;Kelso J
通讯作者：
Kelso J
影响因子：
16
作者：
Bertrand, Mathieu J. M.;Milutinovic, Snezana;Barker, Philip A.
通讯作者：
Barker, Philip A.
DOI：
10.1006/bbrc.2001.5874
发表时间：
2001-11-09
影响因子：
3.1
作者：
Fasshauer, M;Klein, J;Paschke, R
通讯作者：
Paschke, R
DOI：
10.1073/pnas.0700548104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Fukushima, Toru;Matsuzawa, Shu-ichi;Reed, John C.
通讯作者：
Reed, John C.
影响因子：
3.8
作者：
Lee, TH;Yi, W;Her, CT
通讯作者：
Her, CT