The transferrin receptor.

Transferrin receptor (TfR) is a membrane receptor involved in the control of iron supply to the cell through the binding of transferrin, the major iron-carrier protein. This receptor plays a key role in the control of cell proliferation because iron is essential for sustaining ribonucleotide reductase activity, and is the only enzyme that catalyzes the conversion of ribonucleotides to deoxyribonucleotides. Furthermore, TfR is overexpressed in several tumors. The synthesis of the receptor is controlled through an iron-dependent negative feedback in cells where the receptor is involved in the control of cell proliferation, but through a positive feedback in cell types involved in iron storage (monocytes-macrophages). Recent studies have shed light on the molecular basis by which iron regulates TfR expression. Thus, the 3' untranslated region of TfR mRNA contains a cis-acting RNA element, termed the iron-regulatory element (IRE), that interacts with an IRE-binding protein (IRE-BP). The high-affinity interaction between IRE-BP and IRE in the TfR mRNA leads to repression of mRNA degradation and thus to higher synthesis of TfR. Hence, the study of IRE-BP activity will elucidate the mechanisms that modulate TfR expression in normal and malignant cells.