The PfNF-YB transcription factor is a downstream target of melatonin and cAMP signalling in the human malaria parasite Plasmodium falciparum
Version of Record online: 16 JUL 2012
© 2012 John Wiley & Sons A/S
Journal of Pineal Research
Volume 54, Issue 2, pages 145–153, March 2013
How to Cite
Lima, W. R., Moraes, M., Alves, E., Azevedo, M. F., Passos, D. O. and Garcia, C. R. S. (2013), The PfNF-YB transcription factor is a downstream target of melatonin and cAMP signalling in the human malaria parasite Plasmodium falciparum. Journal of Pineal Research, 54: 145–153. doi: 10.1111/j.1600-079X.2012.01021.x
- Issue online: 6 FEB 2013
- Version of Record online: 16 JUL 2012
- Accepted manuscript online: 6 JUN 2012 12:24PM EST
- Received April 17, 2012; Accepted June 1, 2012.
- transcription factor
Abstract: Plasmodium falciparum causes the most severe form of malaria and is responsible for the majority of deaths worldwide. The mechanism of cell cycle control within intra-erythrocytic stages has been examined as a potential means of a promising way to identifying how to stop parasite development in red blood cells. Our group determined that melatonin increases parasitemia in P. falciparum and P. chabaudi through a complex signalling cascade. In vertebrates, melatonin controls the expression of transcription factors, leading us to postulate rather that the indoleamine would affect PfNF-YB expression in human malaria parasites. We show here that PfNF-YB transcription factor is highly expressed and colocalized in the nucleus in mature parasites during intra-erythrocytic stages, thus suggesting an important role in cell division. Moreover, we demonstrate for the first time that melatonin and cAMP modulate the PfNF-YB transcription factor expression in P. falciparum at erythrocytic stages. In addition, PfNF-YB is found to be more ubiquitinated in the presence of melatonin. Finally, the proteasome inhibitor bortezomib is able to modulate PfNF-YB expression as well. Taken together, our dada reinforce the role played by melatonin in the cell cycle control of P. falciparum and point this indolamine as a target to develop new antimalarial drugs.