Signal transduction triggered by iron to induce the nuclear importation of a Myb3 transcription factor in the parasitic protozoan, Trichomonas vaginalis. [Signal Transduction]

September 2nd, 2014 by Hsu, H.-M., Lee, Y., Hsu, P.-H., Liu, H.-W., Chu, C.-H., Chou, Y.-W., Chen, Y.-R., Chen, S.-H., Tai, J.-H.

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, while the latter was also induced by 8-bromo-cAMP. 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, Myb3′s nuclear influx induced by iron or 8-bromo-cAMP was respectively delayed or inhibited by H89, the inhibitor of protein kinase A. Using liquid chromatography-coupled tandem mass spectrometry, Thr156 and Lys143 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 physiology of the parasite than previously thought to encounter environmental changes.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Signal transduction triggered by iron to induce the nuclear importation of a Myb3 transcription factor in the parasitic protozoan, Trichomonas vaginalis. [Signal Transduction]