title: Human Copper Chaperone Atox1 Translocates to the Nucleus but does not Bind DNA In Vitro.
abstract: After Ctr1-mediated cell uptake, copper (Cu) is transported by the cytoplasmic Cu chaperone Atox1 to P1B type ATPases ATP7A and ATP7B in the Golgi network, for incorporation into Cudependent enzymes. Atox1 is a small 68-residue protein that binds Cu in a conserved CXXC motif; it delivers Cu to target domains in ATP7A/B via direct protein-protein interactions. Specific transcription factors regulating expression of the human Cu transport proteins have not been reported although Atox1 was recently suggested to have dual functionality such that it, in addition to its cytoplasmic chaperone function, acts as a transcription factor in the nucleus. To examine this hypothesis, here we investigated the localization of Atox1 in HeLa cells using fluorescence imaging in combination with in vitro binding experiments to fluorescently labeled DNA duplexes harboring the proposed promotor sequence. We found that whereas Atox1 is present in the nucleus in HeLa cells, it does not bind to DNA in vitro. It appears that Atox1 mediates transcriptional regulation via additional (unknown) proteins.
authors.forename: Dana
authors.initials: D
authors.lastname: Kahra
authors.forename: Tanumoy
authors.initials: T
authors.lastname: Mondol
authors.forename: Moritz S
authors.initials: MS
authors.lastname: Niemiec
authors.affiliation: Department of Chemistry, Umea University, Linnaeus Vagen 10, 90187 Umea,, Sweden. pernilla.wittung@chem.umu.se.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
mesh_terms: D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D000079922:Copper Transport Proteins; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D056511:Metallochaperones / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D018832:Molecular Chaperones; D011485:Protein Binding
chemical_list: C474500:ATOX1 protein, human; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper; D004247:DNA