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Iron acquisition is a prerequisite for cell proliferation. The transferrin receptor is the primary mode of iron uptake. This receptor mediates iron uptake through internalization and recycling of the iron carrying serum protein transferrin. Binding of transferrin to its receptor causes rapid internalization into an acidic intracellular compartment where iron dissociates from transferrin. Both the receptor and transferrin are then recycled through the exocytic pathway. The transferrin receptor is expressed in most cells and tissues, especially proliferating cells, and the receptor is expressed as a dimer of identical integral membrane proteins. Transferrin receptor mRNA expression is inversely proportional to iron availability, and this regulation occurs through post-transcriptional control of mRNA stability. Transferrin receptor mRNA contains iron responsive elements (IRE) that are bound by IRE-binding proteins (IRP). The RNA binding of IRPs is dependent on iron levels. Thus, iron deprivation leads to increased RNA binding, which masks the recognition site of endonucleases and stabilizes transferrin receptor mRNA.Western Blotting
