Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins
Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins
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DOI：
10.1073/pnas.93.10.4604
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Belshaw, PJ;Ho, SN;Schreiber, SL
细胞外生长和分化因子通过启动一系列改变细胞内信号蛋白的亚细胞定位的蛋白质关联来诱导细胞核中基因表达的变化。初始事件涉及受体同二聚或异二聚化以及随后将胞质信号蛋白募集至质膜内叶。中间事件涉及蛋白质易位到细胞核中。晚期事件涉及将转录激活剂募集到细胞核中特定基因附近，从而导致基因转录增加。通过使用二聚化的异二聚化学诱导剂来说明在信号传导途径的这三个阶段中的每一个阶段诱导信号的能力，该二聚化导致两个不同靶蛋白之间的邻近关系。
Extracellular growth and differentiation factors induce changes in gene expression in the nucleus by initiating a series of protein associations that alter the subcellular localization of intracellular signaling proteins. Initial events involve receptor homo- or heterodimerization and subsequent recruitment of cytosolic signaling proteins to the inner leaflet of the plasma membrane. Intermediate events involve the translocation of proteins into the nucleus. Late events involve the recruitment of transcriptional activators to the vicinity of specific genes in the nucleus, resulting in increased gene transcription. The ability to induce signals at each of these three phases of signaling pathways is illustrated by the use of a heterodimeric chemical inducer of dimerization that causes a proximal relationship between two different target proteins.