Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors.
Dissecting the signaling events that impact classical nuclear import and target nuclear transport factors.
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DOI：
10.1371/journal.pone.0008420
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发表时间：
2009-12-24
期刊：
影响因子：
3.7
通讯作者：
Stochaj U
中科院分区：
文献类型：
--
作者：
Kodiha M;Tran D;Morogan A;Qian C;Stochaj U
通过MEK→ ERK 1/2和PI 3激酶的信号传导涉及细胞生理学的许多方面，包括氧化剂暴露的存活。氧化剂在许多生理和病理生理过程中发挥作用，其中许多依赖于进出细胞核的转运。然而，氧化应激如何影响核贩运还没有很好的定义。为了更好地理解应激对核质运输的影响，我们将细胞暴露于氧化剂马来酸二乙酯。这种处理激活MEK→ ERK 1/2以及PI 3激酶→Akt级联反应，并触发经典核输入的抑制。为了确定调节核转运的分子机制，我们研究了MEK和PI 3激酶信号传导是否影响关键转运因子的定位。使用最近开发的图像采集和分析工具，在不同的细胞区室中定量importin-α、CAS和核孔蛋白Nup 153和Nup 88的亚细胞分布。这些研究确定了在细胞核和细胞质中以及在核膜中定位转运因子的特定配置文件。我们的研究结果表明，MEK和PI 3激酶信号以及氧化应激控制核运输和运输组件的本地化。此外，应激不仅诱导转运因子分布的变化，而且上调转运因子的翻译后修饰。我们的结果与这样的观点一致，即当细胞暴露于氧化剂时，importin-α、CAS、Nup 153和Nup 88的磷酸化以及Nup 153的O-GlcNAc修饰增加。我们的研究定义了经典核输入的复杂调节，并确定了应激、MEK和PI 3激酶信号传导靶向的关键转运因子。
Signaling through MEK→ERK1/2 and PI3 kinases is implicated in many aspects of cell physiology, including the survival of oxidant exposure. Oxidants play a role in numerous physiological and pathophysiological processes, many of which rely on transport in and out of the nucleus. However, how oxidative stress impacts nuclear trafficking is not well defined. To better understand the effect of stress on nucleocytoplasmic trafficking, we exposed cells to the oxidant diethyl maleate. This treatment activated MEK→ERK1/2 as well as PI3 kinase→Akt cascades and triggered the inhibition of classical nuclear import. To define the molecular mechanisms that regulate nuclear transport, we examined whether MEK and PI3 kinase signaling affected the localization of key transport factors. Using recently developed tools for image acquisition and analysis, the subcellular distributions of importin-α, CAS, and nucleoporins Nup153 and Nup88 were quantified in different cellular compartments. These studies identified specific profiles for the localization of transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress control nuclear trafficking and the localization of transport components. Furthermore, stress not only induced changes in transport factor distribution, but also upregulated post-translational modification of transport factors. Our results are consistent with the idea that the phosphorylation of importin-α, CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when cells are exposed to oxidant. Our studies defined the complex regulation of classical nuclear import and identified key transport factors that are targeted by stress, MEK, and PI3 kinase signaling.
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影响因子：
4.7
作者：
Lee B;Cao R;Choi YS;Cho HY;Rhee AD;Hah CK;Hoyt KR;Obrietan K
通讯作者：
Obrietan K
DOI：
10.1253/circj.cj-08-1082
发表时间：
2009-02
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Heistad DD;Wakisaka Y;Miller J;Chu Y;Pena-Silva R
通讯作者：
Pena-Silva R
影响因子：
12.4
作者：
Kodiha, M;Chu, A;Stochaj, U
通讯作者：
Stochaj, U
DOI：
10.1073/pnas.0803906105
发表时间：
2008-11-04
影响因子：
11.1
作者：
Lai, Kwok-On;Zhao, Yali;Martin, Kelsey C.
通讯作者：
Martin, Kelsey C.
影响因子：
4.8
作者：
Fagerlund, Riku;Melen, Krister;Julkunen, Ilkka
通讯作者：
Julkunen, Ilkka