Kim Inae, Hur Jung, Jeong Sunjoo
Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do 448-701, Republic of Korea.
Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do 448-701, Republic of Korea.
Biochem Biophys Res Commun. 2015 Jan 30;457(1):65-70. doi: 10.1016/j.bbrc.2014.12.052. Epub 2014 Dec 19.
β-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of β-catenin is a critical step for expressing target genes. β-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/β-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the β-catenin protein in the cytoplasm. Thus, Wnt/β-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic β-catenin functions related to HuR-mediated RNA metabolism in cancer cells.
β-连环蛋白是细胞核中经典Wnt信号通路的关键转录激活因子；因此，β-连环蛋白在细胞核中的积累是表达靶基因的关键步骤。β-连环蛋白在癌细胞核中积累，在那里它激活致癌靶基因。Hu抗原R（HuR）是一种RNA结合蛋白，可调节包括RNA稳定性在内的多个转录后过程。因此，细胞质中的HuR蛋白可能通过稳定致癌转录本参与肿瘤发生，但其分子机制仍不清楚。在这里，我们观察到Wnt/β-连环蛋白信号通路诱导HuR蛋白输出，而HuR过表达促进β-连环蛋白在细胞质中的积累。因此，过表达HuR可降低细胞核中Wnt/β-连环蛋白介导的转录活性。这些结果表明，在癌细胞中，β-连环蛋白在细胞质中具有与HuR介导的RNA代谢相关的新的、未被描述的功能。
