Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
Cell Rep. 2020 Nov 17;33(7):108396. doi: 10.1016/j.celrep.2020.108396.
Zyxin is a cytoskeletal LIM-domain protein that regulates actin cytoskeleton assembly and gene expression. In the present work, we find that zyxin downregulation in Xenopus laevis embryos reduces the expression of numerous genes that regulate cell differentiation, but it enhances that of several genes responsible for embryonic stem cell status, specifically klf4, pou5f3.1, pou5f3.2, pou5f3.3, and vent2.1/2. For pou5f3 family genes (mammalian POU5F1/OCT4 homologs), we show that this effect is the result of mRNA stabilization due to complex formation with the Y-box protein Ybx1. When bound to Ybx1, zyxin interferes with the formation of these complexes, thereby stimulating pou5f3 mRNA degradation. In addition, in zebrafish embryos and human HEK293 cells, zyxin downregulation increases mRNA levels of the pluripotency genes KLF4, NANOG, and POU5F1/OCT4. Our findings indicate that zyxin may play a role as a switch among morphogenetic cell movement, differentiation, and embryonic stem cell status.
锌指蛋白交联物（Zyxin）是一种细胞骨架 LIM 结构域蛋白，可调节肌动蛋白细胞骨架的组装和基因表达。在本工作中，我们发现非洲爪蟾胚胎中 Zyxin 的下调会降低许多调节细胞分化的基因的表达，但会增强几个负责胚胎干细胞状态的基因的表达，特别是 klf4、pou5f3.1、pou5f3.2、pou5f3.3 和 vent2.1/2。对于 pou5f3 家族基因（哺乳动物 POU5F1/OCT4 同源物），我们表明这种效应是由于与 Y 盒蛋白 Ybx1 形成复合物导致 mRNA 稳定的结果。当与 Ybx1 结合时，Zyxin 会干扰这些复合物的形成，从而刺激 pou5f3 mRNA 的降解。此外，在斑马鱼胚胎和人 HEK293 细胞中，Zyxin 的下调会增加多能性基因 KLF4、NANOG 和 POU5F1/OCT4 的 mRNA 水平。我们的研究结果表明，Zyxin 可能在形态发生细胞运动、分化和胚胎干细胞状态之间充当开关。
