品牌：Virogen

貨號：101-A

代理：靶點(diǎn)科技

名稱：ANTI-GLUTATHIONE MAB 100

論文題目：Glutaredoxin-1 regulates TRAF6 activation and the IL-1 receptor/TLR4 signalling

期刊：Biochemical and Biophysical Research Communications (BBRC). Volume 403, Issues 3–4, 17 December 2010, Pages 335-339

摘要：戊二醇-1 （GRX-1） 是一種細(xì)胞質(zhì)酶，對抗氧化防御系統(tǒng)有很大貢獻(xiàn)。它催化谷胱甘肽-蛋白質(zhì)混合二硫化物的可逆還原，這一過程稱為脫谷胱甘肽化。在這里，我們通過使用 HEK293 和 HeLa 細(xì)胞中的 RNA 干擾 （RNAi） 研究了 GRX-1 在白細(xì)胞介素-1/Toll 樣受體 4 （IL-1R/TLR4） 觸發(fā)的通路中的作用。TNF 受體相關(guān)因子 6 （TRAF6） 是一種中間信號分子，參與白細(xì)胞介素-1/Toll 樣受體 （IL-1R/TLR） 家族成員的信號轉(zhuǎn)導(dǎo)。TRAF6 具有 E3 泛素連接酶活性，該活性取決于氨基末端非常有趣的新基因 （RING） 手指基序的完整性。受體激活后，TRAF6 發(fā)生 K63 連接的自體多泛素化，介導(dǎo)蛋白質(zhì)-蛋白質(zhì)相互作用和信號傳播。我們的數(shù)據(jù)表明，IL-1R 和 TLR4 介導(dǎo)的 NF-κB 誘導(dǎo)在 GRX-1 敲低細(xì)胞中嚴(yán)重降低。我們發(fā)現(xiàn) TRAF6 的無名指基序在正常條件下是 S-谷胱甘肽化的。此外，在 IL-1 刺激下，TRAF6 經(jīng)歷由 GRX-1 催化的去谷胱甘肽化。TRAF6 的去谷胱氨?；瘜ζ渥詣佣喾核鼗碗S后的激活至關(guān)重要。綜上所述，我們的研究結(jié)果揭示了另一種受 S-谷胱甘肽化影響的信號分子，并揭示了 GRX-1 在 IL-1R/TLR 對 NF-κB 的 TRAF6 依賴性激活中的關(guān)鍵作用。

Abstract:

Glutaredoxin-1 (GRX-1) is a cytoplasmic enzyme that highly contributes to the antioxidant defense system. It catalyzes the reversible reduction of glutathione–protein mixed disulfides, a process called deglutathionylation. Here, we investigated the role of GRX-1 in the pathway triggered by interleukin-1/Toll-like receptor 4 (IL-1R/TLR4) by using RNA interference (RNAi) in HEK293 and HeLa cells. TNF receptor-associated factor 6 (TRAF6) is an intermediate signalling molecule involved in the signal transduction by members of the interleukin-1/Toll-like receptor (IL-1R/TLR) family. TRAF6 has an E3 ubiquitin ligase activity which depends on the integrity of an amino-terminal really interesting new gene (RING) finger motif. Upon receptor activation, TRAF6 undergoes K63-linked auto-polyubiquitination which mediates protein–protein interactions and signal propagation. Our data showed that IL-1R and TLR4-mediated NF-κB induction was severely reduced in GRX-1 knockdown cells. We found that the RING-finger motif of TRAF6 is S-glutathionylated under normal conditions. Moreover, upon IL-1 stimulation TRAF6 undergoes deglutathionylation catalyzed by GRX-1. The deglutathionylation of TRAF6 is essential for its auto-polyubiquitination and subsequent activation. Taken together, our findings reveal another signalling molecule affected by S-glutathionylation and uncover a crucial role for GRX-1 in the TRAF6-dependent activation of NF-κB by IL-1R/TLRs.

谷胱甘肽檢測抗體：