title: Signal transduction triggered by iron to induce the nuclear importation of a Myb3 transcription factor in the parasitic protozoan Trichomonas vaginalis.
abstract: Iron was previously shown to induce rapid nuclear translocation of a Myb3 transcription factor in the protozoan parasite, Trichomonas vaginalis. In the present study, iron was found to induce a transient increase in cellular cAMP, followed by the nuclear influx of Myb3, whereas the latter was also induced by 8-bromo-cyclic AMP. Iron-inducible cAMP production and nuclear influx of Myb3 were inhibited by suramin and SQ22536, respective inhibitors of the Gα subunit of heterotrimeric G proteins and adenylyl cyclases. In contrast, the nuclear influx of Myb3 induced by iron or 8-bromo-cAMP was delayed or inhibited, respectively, by H89, the inhibitor of protein kinase A. Using liquid chromatography-coupled tandem mass spectrometry, Thr(156) and Lys(143) in Myb3 were found to be phosphorylated and ubiquitinated, respectively. These modifications were induced by iron and inhibited by H89, as shown by immunoprecipitation-coupled Western blotting. Iron-inducible ubiquitination and nuclear influx were aborted in T156A and K143R, but T156D was constitutively ubiquitinated and persistently localized to the nucleus. Myb3 was phosphorylated in vitro by the catalytic subunit of a T. vaginalis protein kinase A, TvPKAc. A transient interaction between TvPKAc and Myb3 and the phosphorylation of both proteins were induced in the parasite shortly after iron or 8-bromo-cAMP treatment. Together, these observations suggest that iron may induce production of cAMP and activation of TvPKAc, which then induces the phosphorylation of Myb3 and subsequent ubiquitination for accelerated nuclear influx. It is conceivable that iron probably exerts a much broader impact on the physiology of the parasite than previously thought to encounter environmental changes.
authors.affiliation: From the Division of Infectious Diseases, Institute of Biomedical Sciences and.
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Hsu
authors.affiliation: From the Division of Infectious Diseases, Institute of Biomedical Sciences and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lee
authors.affiliation: the Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelun 20224, Taiwan, and.
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.affiliation: From the Division of Infectious Diseases, Institute of Biomedical Sciences and.
authors.forename: Hsing-Wei
authors.initials: HW
authors.lastname: Liu
authors.affiliation: From the Division of Infectious Diseases, Institute of Biomedical Sciences and.
authors.forename: Chien-Hsin
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Research Center of Agriculture and Biotechnology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chou
authors.affiliation: Research Center of Agriculture and Biotechnology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yet-Ran
authors.initials: YR
authors.lastname: Chen
authors.affiliation: the Department of Chemistry, National Chen Kung University, Tainan 70101, Taiwan.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: From the Division of Infectious Diseases, Institute of Biomedical Sciences and taijh@gate.sinica.edu.tw.
authors.forename: Jung-Hsiang
authors.initials: JH
authors.lastname: Tai
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics; D010766:Phosphorylation; D015800:Protozoan Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014246:Trichomonas vaginalis / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D009841:Oligonucleotides; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D000242:Cyclic AMP; D007501:Iron; D019204:GTP-Binding Proteins; D008239:Lysine
keywords: G Protein; Iron; Myb3; Nuclear Translocation; Phosphorylation; Protein Kinase A (PKA); Signal Transduction; Trichomonas vaginalis; Ubiquitylation (Ubiquitination)