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Excess capacity of the iron regulatory protein system.

Excess capacity of the iron regulatory protein system. Research Abstract Details 

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  • Excess capacity of the iron regulatory protein system. Abstract Text:

    wei wangWei Wang,xiumin diXiumin Di,ralph b d'agostinoRalph B D'Agostino,suzy v tortiSuzy V Torti,frank m tortiFrank M Torti,

    Iron regulatory proteins (IRP1 and IRP2) are master regulators of cellular iron metabolism. IRPs bind to iron-responsive elements (IREs) present in the untranslated regions of mRNAs encoding proteins of iron storage, uptake, transport, and export. Because simultaneous knockout of IRP1 and IRP2 is embryonically lethal, it has not been possible to use dual knockouts to explore the consequences of loss of both IRP1 and IRP2 in mammalian cells. In this report, we describe the use of small interfering RNA to assess the relative contributions of IRP1 and IRP2 in epithelial cells. Stable cell lines were created in which either IRP1, IRP2, or both were knocked down. Knockdown of IRP1 decreased IRE binding activity but did not affect ferritin H and transferrin receptor 1 (TfR1) expression, whereas knockdown of IRP2 marginally affected IRE binding activity but caused an increase in ferritin H and a decrease in TfR1. Knockdown of both IRPs resulted in a greater reduction of IRE binding activity and more severe perturbation of ferritin H and TfR1 expression compared with single IRP knockdown. Even though the knockdown of IRP-1, IRP-2, or both was efficient, resulting in nondetectable protein and under 5% of wild type levels of mRNA, all stable knockdowns retained an ability to modulate ferritin H and TfR1 appropriately in response to iron challenge. However, further knockdown of IRPs accomplished by transient transfection of small interfering RNA in stable knockdown cells completely abolished the response of ferritin H and TfR1 to iron challenge, demonstrating an extensive excess capacity of the IRP system.

    Excess capacity of the iron regulatory protein system. Publishing Authors By Initials

    w wangW Wang,x diX Di,rb d'agostinoRB D'Agostino,sv tortiSV Torti,fm tortiFM Torti,

    For similar abstracts research abstracts see: abstracts research

    PUBMED ID PMID:

    MEDLINE DATE:

    Excess capacity of the iron regulatory protein system. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 24650-9

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 28

    MONTH: 06

    YEAR: 2007

    Excess capacity of the iron regulatory protein system. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    Excess capacity of the iron regulatory protein system. Keywords Mesh Terms:

    KEYWORDS: Reverse Transcriptase Polymerase Chain R

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Excess capacity of the iron regulatory protein system. Information

    Substance Name: Iron Regulatory Protein 2

    Registry Number: EC 4.2.1.3

    Grant and Affiliation Information for Excess capacity of the iron regulatory protein system.

    AFFILIATION: Department of Cancer Biology, Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDDK

    GRANT: R37 DK42412

    ACRONYM: DK

    MEDLINETA: J Biol Chem

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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