The small-molecule iron transport inhibitor ferristatin/NSC306711 promotes degradation of the transferrin receptor
Graduate School of Biomedical Sciences; Department of Genetics and Complex Diseases
Life Sciences | Medicine and Health Sciences
Iron delivery by transferrin (Tf) is accomplished through clathrin-mediated endocytosis of Tf receptors. The small molecule NSC306711 inhibits iron uptake from the Tf-TfR pathway. Here we show that the drug's mechanism of action is to induce internalization and degradation of unoccupied Tf receptors through an unexpected endocytic pathway. Unlike classical clathrin-mediated Tf receptor endocytosis, internalization promoted by NSC306711 is independent of clathrin and dynamin, and is sensitive to the cholesterol-depleting agents filipin and nystatin. The finding of this cholesterol-dependent Tf receptor internalization pathway through use of the small-molecule inhibitor sheds light on the pleiotropic nature of membrane trafficking dynamics and adds a complex dimension to our understanding of receptor regulation. Because of its unusual properties to inhibit iron uptake, we refer to NSC306711 as "ferristatin."
DOI of Published Version
Chem Biol. 2008 Jul 21;15(7):647-53. Link to article on publisher's site
Chemistry and biology
Horonchik L, Wessling-Resnick M. (2008). The small-molecule iron transport inhibitor ferristatin/NSC306711 promotes degradation of the transferrin receptor. GSBS Student Publications. https://doi.org/10.1016/j.chembiol.2008.05.011. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1541