Iron plays an essential role in numerous enzymatic processes. However, Fe+3 can catalyze dangerous oxidative reactions. Thus, all living organisms have developed proteins to transport, store and scavenge this indispensable yet hazardous metal. Numerous studies in vertebrates have associated the development of infection and neoplasia with excessive exposure to iron. Vertebrate data indicate that ferritin, an iron- binding protein, plays an essential role in the maintenance of cellular iron homeostasis in differentiating and malignant cells. The regulation of ferritin expression in these cases in mainly at the transcriptional level. Currently, the actual molecular machinery that activates this response remains unknown. Recent data attest to similarities between insect and vertebrate iron metabolism. Knowledge of insect iron metabolism however is limited. Our preliminary data indicated that transcriptional control is germane to the expression of ferritin in the yellow fever mosquito Aedes aegypti. The objective of this application is to dissect the transcriptional regulation of the mosquito A.aegypti ferritin. To accomplish the objective of this application, we will pursue three specific aims: 1) Obtain genomic clone containing approximately 20 kilobases of the 5' upstream region of the ferritin gene, 2) Map the cis-regulatory elements at the 5' upstream region and/or within the ferritin gene, 3) Partially identify of trans-regulatory factors.
| Pham, Daphne Q D; Winzerling, Joy J (2010) Insect ferritins: Typical or atypical? Biochim Biophys Acta 1800:824-33 |
