Mediated nuclear import and export of TAZ and the underlying molecular requirements

被引：74

作者：

Kofler, Michael ^{[1
]}

Speight, Pam ^{[1
]}

Little, Darby ^{[1
]}

Di Ciano-Oliveira, Caterina ^{[1
]}

Szaszi, Katalin ^{[1
,2
]}

Kapus, Andras ^{[1
,2
,3
]}

机构：

[1] Univ Toronto, St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON M5B 1T8, Canada

[2] Univ Toronto, Dept Surg, Toronto, ON M5B 1T8, Canada

[3] Univ Toronto, Dept Biochem, Toronto, ON M5B 1T8, Canada

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

TEAD TRANSCRIPTION FACTORS; HIPPO PATHWAY; LOCALIZATION SIGNAL; TGF-BETA; MYOFIBROBLAST TRANSITION; YAP ONCOPROTEIN; RAN/TC4; GTPASE; GROWTH-CONTROL; MESSENGER-RNA; LEPTOMYCIN B;

D O I：

10.1038/s41467-018-07450-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nucleocytoplasmic distribution of Yap/TAZ is regulated by the Hippo pathway and the cytoskeleton. While interactions with cytosolic and nuclear "retention factors" (14-3-3 and TEAD) are known to control their localization, fundamental aspects of Yap/TAZ shuttling remain undefined. It is unclear if translocation occurs only by passive diffusion or via mediated transport, and neither the potential nuclear localization and efflux signals (NLS, NES) nor their putative regulation have been identified. Here we show that TAZ cycling is a mediated process and identify the underlying NLS and NES. The C-terminal NLS, representing a new class of import motifs, is necessary and sufficient for efficient nuclear uptake via a RAN-independent mechanism. RhoA activity directly stimulates this import. The NES lies within the TEAD-binding domain and can be masked by TEAD, thereby preventing efflux. Thus, we describe a RhoA-regulated NLS, a TEAD-regulated NES and propose an improved model of nucleocytoplasmic TAZ shuttling beyond "retention".

引用

页数：15