Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function.

Abstract:

:Nucleocytoplasmic transport of transcription factors is essential in eukaryotes. We previously reported the presence of two functional NLSs in the homeodomain protein, aristaless-related homeobox (Arx) protein, which is a key transcriptional repressor of LMO1, SHOX2, and PAX4 during development. NLS2, that overlaps the homeodomain, is recognized directly by multiple importin βs, but not by importin αs. In this study, we found that the N-terminal NLS1 of Arx is targeted by multiple importin α proteins, including importin α3 and α5. Both in vivo and in vitro assays demonstrated that nuclear import of Arx via NLS1 is mediated by the importin α/β pathway. Mutagenesis analysis indicated that two basic amino acids, (84)K and (87)R, are essential to the function of NLS1, and that their mutation prevents interactions of Arx with importin αs. Interestingly, inhibition of nuclear import of Arx via NLS1 clearly attenuates its ability of transcriptional repression, suggesting that nuclear import of Arx via NLS1 contributes to its transcriptional function.

journal_name

Mol Cell Biochem

authors

Ye W,Lin W,Tartakoff AM,Ma Q,Tao T

doi

10.1007/s11010-013-1706-7

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

221-31

issue

1-2

eissn

0300-8177

issn

1573-4919

journal_volume

381

pub_type

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