FBXL5: Sensor and Regulator of Mammalian Iron Homeostasis

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Title: FBXL5: Sensor and Regulator of Mammalian Iron Homeostasis
Author: Salahudeen, Ameen Abdulla
Abstract: While iron is an important cofactor for many proteins , the chemical properties of iron that favor its biological roles can lead to toxic side reactions that damage macromolecules . Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of gene products responsible for iron uptake , release , utilization , and storage . This process is mediated by Iron Regulatory Proteins (IRPs ) that bind to Iron Responsive Elements (IREs ) in the mRNAs of these genes . When iron bioavailability is low IRPs bind IREs within these mRNAs , affecting their subsequent translation or stability . When cellular free iron availability is high , IRPs are preferentially degraded by the proteasome . An SCF E3 ubiquitin ligase complex containing the FBXL5 protein regulates this process as a function of cellular iron and oxygen concentrations . This process occurs through the stability of FBXL5 , which accumulates under iron and oxygen replete conditions and is targeted for degradation upon iron depletion . FBXL5 contains an iron - and oxygen -sensing hemerythrin domain that acts as a ligand -binding regulatory switch mediating its stability . As a result , FBXL5 directly senses iron and oxygen levels to serve as a regulator of cellular iron homeostasis .
URI: http : / /hdl .handle .net /2152 .5 /883
Date: 2011-08-26

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FBXL5: Sensor and Regulator of Mammalian Iron Homeostasis. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /883 .

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