The helicase, DDX3X, interacts with poly(A)-binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading.
The helicase, DDX3X, interacts with poly(A)-binding protein 1 (PABP1) and caprin-1 at the leading edge of migrating fibroblasts and is required for efficient cell spreading.
复制标题
解旋酶DDX3X在迁移成纤维细胞的前沿与poly（a）结合蛋白1（PABP1）和Caprin-1相互作用，对于有效的细胞扩散是必需的。
DOI：
10.1042/bcj20170354
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发表时间：
2017-08-30
期刊：
影响因子：
--
通讯作者：
Morley SJ
中科院分区：
文献类型：
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作者：
Copsey AC;Cooper S;Parker R;Lineham E;Lapworth C;Jallad D;Sweet S;Morley SJ
DDX3X是一种解旋酶，可以直接与mRNA和翻译起始因子相互作用，调节含有5‘非翻译区的mRNAs的选择性翻译。这种活性调节控制细胞周期进程的mRNAs的表达，以及调节肌动蛋白动力学的mRNAs的表达，有助于细胞的黏附和运动。此前，我们已经证明核糖体和翻译启动因子定位于迁移的成纤维细胞的前沿，在活跃的翻译核糖体丰富的区域，从而在扩散过程中促进细胞前沿的ArpC2和rac1蛋白的稳定水平。由于DDX3X可以调节rac1水平、细胞运动和转移，我们用许多互补的方法研究了DDX3X蛋白的相互作用和定位。我们现在证明了DDX3X可以与Poly(A)结合蛋白1和Caprin-1在扩散细胞的前沿物理上相互作用和共定位。此外，由于DDX3X的缺失导致细胞运动能力下降，这在DDX3X、Caprin-1和迁移细胞前沿的启动因子之间提供了一种功能联系，以促进细胞的迁移和扩散。
DDX3X, a helicase, can interact directly with mRNA and translation initiation factors, regulating the selective translation of mRNAs that contain a structured 5′ untranslated region. This activity modulates the expression of mRNAs controlling cell cycle progression and mRNAs regulating actin dynamics, contributing to cell adhesion and motility. Previously, we have shown that ribosomes and translation initiation factors localise to the leading edge of migrating fibroblasts in loci enriched with actively translating ribosomes, thereby promoting steady-state levels of ArpC2 and Rac1 proteins at the leading edge of cells during spreading. As DDX3X can regulate Rac1 levels, cell motility and metastasis, we have examined DDX3X protein interactions and localisation using many complementary approaches. We now show that DDX3X can physically interact and co-localise with poly(A)-binding protein 1 and caprin-1 at the leading edge of spreading cells. Furthermore, as depletion of DDX3X leads to decreased cell motility, this provides a functional link between DDX3X, caprin-1 and initiation factors at the leading edge of migrating cells to promote cell migration and spreading.