Nrf2:INrf2 (Keap1) signaling in oxidative stress.
Nrf2:INrf2 (Keap1) signaling in oxidative stress.
复制标题
NRF2：氧化应激中的INRF2（KEAP1）信号传导。
DOI：
10.1016/j.freeradbiomed.2009.07.035
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发表时间：
2009-11-01
影响因子：
7.4
通讯作者：
Jaiswal, Anil K.
中科院分区：
文献类型：
--
作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
NRF2：INRF2(Keap1)是化学和辐射诱导的氧化和亲电应激的细胞感受器。NRF2是一种核转录因子，控制着一系列编码解毒酶和抗氧化蛋白的防御基因的表达和协调诱导。这是一个对细胞保护和细胞生存至关重要的机制。NRF2被抑制物INRF2保留在细胞质中。INrf2作为CUL3/Rbx1介导的Nrf2降解的适配器。作为对氧化/亲电应激的响应，Nrf2通过不同的早期和延迟机制被开启和关闭。INrf2cysteine 151的氧化/亲电修饰和/或Nrf2serine40的PKC磷酸化导致Nrf2从INrf2逃逸或释放。NRF2稳定并移位到细胞核，与未知蛋白质形成异二聚体，并与抗氧化反应元件(ARE)结合，导致基因表达的协调激活。从暴露到开启核进口NRF2只需不到15分钟的时间。紧随其后的是一种延迟机制的激活，该机制控制Nrf2基因表达的激活关闭。Gsk3β使Fyn在未知苏氨酸残基上磷酸化(S)，导致Fyn的核定位。Fyn使Nrf2酪氨酸568磷酸化，导致Nrf2的核输出，与INrf2结合并降解Nrf2。Nrf2的开启和关闭保护细胞免受自由基损伤，防止细胞凋亡，促进细胞存活。
Nrf2:INrf2(Keap1) are cellular sensors of chemical and radiation induced oxidative and electrophilic stress. Nrf2 is a nuclear transcription factor that controls the expression and coordinated induction of a battery of defensive genes encoding detoxifying enzymes and antioxidant proteins. This is a mechanism of critical importance for cellular protection and cell survival. Nrf2 is retained in the cytoplasm by an inhibitor INrf2. INrf2 functions as an adapter for Cul3/Rbx1 mediated degradation of Nrf2. In response to oxidative/electrophilic stress, Nrf2 is switched on and then off by distinct early and delayed mechanisms. Oxidative/electrophilic modification of INrf2cysteine151 and/or PKC phosphorylation of Nrf2serine40 results in the escape or release of Nrf2 from INrf2. Nrf2 is stabilized and translocates to the nucleus, forms heterodimers with unknown proteins, and binds antioxidant response element (ARE) that leads to coordinated activation of gene expression. It takes less than fifteen minutes from the time of exposure to switch on nuclear import of Nrf2. This is followed by activation of a delayed mechanism that controls switching off of Nrf2 activation of gene expression. GSK3β phosphorylates Fyn at unknown threonine residue(s) leading to nuclear localization of Fyn. Fyn phosphorylates Nrf2tyrosine568 resulting in nuclear export of Nrf2, binding with INrf2 and degradation of Nrf2. The switching on and off of Nrf2 protect cells against free radical damage, prevents apoptosis and promotes cell survival.
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影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
DOI：
10.1073/pnas.0813361106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Chen, Pei-Chun;Vargas, Marcelo R.;Johnson, Jeffrey A.
通讯作者：
Johnson, Jeffrey A.
影响因子：
8
作者：
Dhakshinamoorthy, S;Jaiswal, AK
通讯作者：
Jaiswal, AK
影响因子：
4.1
作者：
Balogun, E;Hoque, M;Motterlini, R
通讯作者：
Motterlini, R
DOI：
10.1006/bbrc.1997.6943
发表时间：
1997-07-18
影响因子：
3.1
作者：
Itoh, K;Chiba, T;Nabeshima, Y
通讯作者：
Nabeshima, Y