大分子(蛋白质和核酸)在细胞核质间的分布是真核细胞中最重要的生理功能之一,它在信号传递,基因转录与调控,信使RNA的分布和核糖体的组装及分布等生理过程中起关键的调控作用。
Arx蛋白质是一个与细胞分化和组织发育中至关重要的含homeodomain转录因子,它的功能正常与否与脑,胰腺和睾丸的发育和功能密切相关。厦门大学陶涛教授实验室首次系统地研究了Arx通过不同入核途径在细胞核定位的分子机理和及其调控方式,对进一步研究Arx的生理功能提供了重要的帮助。(生物谷Bioon.com)
生物谷推荐原始出处:
JBC, published June 3, 2009 as doi:10.1074/jbc.M109.004242
The roles of multiple importins for nuclear import of murine aristaless-related homeobox protein
Wenbo Lin1, Wenduo Ye1, Lanlan Cai1, Xinyi Meng1, Guifen Ke1, Caoxin Huang1, Zi Peng1, Yinhua Yu2, Jeffrey A. Golden3, Alan M. Tartakoff4, and Tao Tao15
From the 1 Xiamen University, China; , 2 University of Houston, China; , 3 University of Pennsylvania, China; , 4 Case Western Reserve University, China
Nuclear import of proteins with nuclear localization signals (NLSs) is mediated by shuttling carriers, the importins. Some cargoes display more than a single NLS, and among these are homeodomain proteins such as Arx, which is critical for development of multiple tissues. Arx has two functional NLSs. The present studies show that several pathways can import Arx via its NLS2, which is within its DNA-binding homeodomain. Using an in vitro nuclear import assay we show that import of Arx via NLS2 can be mediated by importin β1, importin 9 or importin 13, with binding being strongest to importin β1. All binding is sensitive to RanGTP. Experiments based on precise domain deletions indicate that NLS2 binds impβ1, imp9 and imp13 and includes both an importin-binding subdomain and a regulatory subdomain with arginine residues being important for function. Moreover, Arx can be co-precipitated with these importins when NLS2 is present. Although nuclear import of Arx can be mediated by these three importin βs, importin β1 seems to play the major role, judging from in vivo siRNA ablations and the in vitro import assay. This is the first evidence to show the role of importin β1 in nuclear import of paired-type homeodomain proteins. We propose a novel and possibly quite general mechanism for nuclear import of paired-type homeodomain proteins which are critical for development.