A team of scientists led by Lei ZHANG at the Shanghai Institute of Biochemistry & Cell Biology, Chinese Academy of Sciences, have identified a potential nuclear localization signal at the N-terminal end of Yorkie as well as a critical role of Importin α1 in Yorkie nuclear import.
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 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.
Lei ZHANG and colleagues demonstrated that the N-terminal 1-55 amino acids of Yorkie may serve as its NLS and is essential for Yorkie’s function and localization. By mass spectrometry and biochemistry analyses, they found that Importin α1 can directly interact with Yorkie N-terminus and drive Yorkie into the nucleus. Further experiments show that the amino acid R15 of Yki is a critical site for Yorkie nuclear import. Moreover, they show that the upstream component Hippo can inhibit Importin α1-mediated Yorkie nuclear import.
This work entitled “Importin α1 mediates Yorkie nuclear import via N-terminal non-canonical nuclear localization signal” was published online by Journal of Biological Chemistry on 17 February 2016.
This work was supported by grants from Chinese Academy of Sciences, the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.
Keywords: Hippo signaling, Yorkie, Importin
CONTACT:
ZHANG Lei, Principal Investigator, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Email: rayzhang@sibcb.ac.cn. Phone: +86-21-54921336.
Figure. A model of the regulation of Yorkie nuclear import (Image provided by ZHANG Lei’s Group)
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