Importin α1 Mediates Yorkie Nuclear Import via an N-terminal Non-canonical Nuclear Localization Signal

作者：Shimin Wang, Yi Lu, Meng-Xin Yin, Chao Wang, Wei Wu, Jinhui Li, Wenqing Wu, Ling Ge, Lianxin Hu, Yun Zhao, Lei Zhang · 发表于：Journal of Biological Chemistry · 年份：2016 · DOI：10.1074/jbc.m115.700823 · 被引用次数：54 · 研究领域：Hippo pathway signaling and YAP/TAZ、RNA Research and Splicing、Nuclear Structure and Function

The Hippo signaling pathway controls organ size by orchestrating cell proliferation and apoptosis. When the Hippo pathway was inactivated, the transcriptional co-activator Yorkie translocates into the nucleus and forms a complex with transcription factor Scalloped to promote the expression of Hippo pathway target genes. Therefore, the nuclear translocation of Yorkie is a critical step in Hippo signaling. Here, we provide evidence that the N-terminal 1-55 amino acids of Yorkie, especially Arg-15, were essential for its nuclear localization. By mass spectrometry and biochemical analyses, we found that Importin α1 can directly interact with the Yorkie N terminus and drive Yorkie into the nucleus. Further experiments show that the upstream component Hippo can inhibit Importin α1-mediated Yorkie nuclear import. Taken together, we identified a potential nuclear localization signal at the N-terminal end of Yorkie as well as a critical role for Importin α1 in Yorkie nuclear import.