Nuclear estrogen receptors co-activation mechanisms.
Nuclear estrogen receptors co-activation mechanisms.
复制标题
核雌激素受体共激活机制。
DOI：
10.2174/09298673113209990006
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发表时间：
2013
影响因子：
4.1
通讯作者：
D. Matosiuk
中科院分区：
文献类型：
--
作者：
M. Skrzypczak;L. Kapka;M. Cyranka;O. Treeck;A. Wrobel;D. Matosiuk
雌激素在开启转录事件中起着非常重要的作用，这是通过来自细胞外部的信息激活细胞壁中作为受体或通道的一级介质的最后一步。长期以来，细胞向细胞核传递信息的确切逐步机制尚不清楚。目前有许多新信息可供使用。磷酸化步骤似乎非常重要，因此目标蛋白脱敏。所有肽激酶，特别是丝氨酸和苏氨酸，如蛋白激酶A和C、RAS和MAP激酶、细胞周期素激酶都是潜在或已证实的生物靶标。除此之外，转录复合物的元件如p160.SRC-1、组蛋白乙酰转移酶和组蛋白脱乙酰酶、CBP/p300、TRAP/DRIP、NSD1、PPARγ/PGC-1、NCOR1、SMRT、REA也被发现有用。最后，雌激素能够激活其他受体，即芳烃受体（AhR）和雌激素受体相关蛋白（ERR）。众所周知，许多类型的癌症都与核雌激素受体的直接或间接过度激活有关，因此抑制它们在许多与雌激素相关的癌症中至关重要。了解此类复合物中的相互作用将有助于开发新的、更好的多靶点治疗方法，并找到具有更好药理学和药代动力学特性的新配体。
Estrogens play very important role in opening the transcription event, which is a final step of activation of the first order mediators as receptors or channels in the cell wall by information coming from the outside of the cell. For the long time the exact step by step mechanism of cellular transfer of information to the cell nuclei was not known. Currently many new informations are available. Very important seems the step of phosphorylation and therefore desensitization of the target proteins. All peptide kinases, especially serine and threonine, like protein kinases A and C, RAS and MAP kinases, cycline kinases are potential or confirmed biological targets. Except them elements of the transcription complexes like p160.SRC-1, histon acetyltransferase and histon deacetylase, CBP/p300, TRAP/DRIP, NSD1, PPARγ/PGC-1, NCOR1, SMRT, REA were also found useful. Finally estrogens are able to activate other receptors, namely aryl hydrocarbon receptors (AhR) and estrogen receptor related proteins (ERR). It is well known that many types of cancer are related to the direct or indirect excessive activation of nuclear estrogen receptors, therefore their inhibition could be crucial in many estrogen-related cancers. Understanding the interactions in such complexes would help in developing new and better multi-target cures and finding new ligands with better pharmacological and pharmacokinetic properties.