title: 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.
authors.affiliation: Xiamen University School of Life Sciences, Xiamen, Fujian, China.
authors.forename: Wenduo
authors.initials: W
authors.lastname: Ye
authors.forename: Wenbo
authors.initials: W
authors.lastname: Lin
authors.forename: Alan M
authors.initials: AM
authors.lastname: Tartakoff
authors.forename: Qilin
authors.initials: Q
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D028901:alpha Karyopherins / Q000378:metabolism
chemical_list: C469265:ARX protein, mouse; D018398:Homeodomain Proteins; D019913:Nuclear Localization Signals; D012097:Repressor Proteins; D014157:Transcription Factors; D028901:alpha Karyopherins