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

Molecular and cellular biochemistry

PubMedID: 23771350

Ye W, Lin W, Tartakoff AM, Ma Q, Tao T. Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function. Mol Cell Biochem. 2013;381(1-2):221-31.
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 ßs, but not by importin as. In this study, we found that the N-terminal NLS1 of Arx is targeted by multiple importin a proteins, including importin a3 and a5. Both in vivo and in vitro assays demonstrated that nuclear import of Arx via NLS1 is mediated by the importin a/ß 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 as. 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.