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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4287-4293. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-06-2477. This Article Full Text (PDF) All Versions of this Article: 2004-06-2477v1 104/13/4287    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Johnson, M. B. Articles by Enns, C. A. Search for Related Content PubMed PubMed Citation Articles by Johnson, M. B. Articles by Enns, C. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 30, 2004 Accepted August 4, 2004 Regulation of transferrin receptor 2 by transferrin: diferric transferrin regulates transferrin receptor 2 protein stability Martha B. Johnson and Caroline A. Enns* * Corresponding author; email: ennsca{at}ohsu.edu. Transferrin receptor 2 (TfR2) is a type-II transmembrane protein expressed in hepatocytes that binds iron-bound transferrin (Tf). Mutations in TfR2 cause one form of hereditary hemochromatosis, a disease in which excessive absorption of dietary iron can lead to liver cirrhosis, diabetes, arthritis, and heart failure. The function of TfR2 in iron homeostasis is unknown. We have studied the regulation of TfR2 in HepG2 cells. Western blot analysis shows that TfR2 increases in a time- and dose-dependent manner after addition of diferric Tf to the culture medium. In cells exposed to diferric Tf, the amount of TfR2 returns to control levels within 8 hours after removal of diferric Tf from the medium. However, TfR2 does not increase when non-Tf bound iron (FeNTA) or apoTf is added to the medium. The response to diferric Tf appears to be hepatocyte specific. Real-time qRT-PCR analysis shows that TfR2 mRNA levels do not change in cells exposed to diferric Tf. Rather, the increase in TfR2 is due to an increase in the half-life of TfR2 protein in cells exposed to diferric Tf. Our results support a role for TfR2 in monitoring iron levels by sensing changes in the concentration of diferric Tf. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Is TfR2 the iron sensor? Tomas Ganz Blood 2004 104: 3839-3840. [Full Text] [PDF] This article has been cited by other articles: C. E. Herbison, K. Thorstensen, A. C. G. Chua, R. M. Graham, P. Leedman, J. K. Olynyk, and D. Trinder The role of transferrin receptor 1 and 2 in transferrin-bound iron uptake in human hepatoma cells Am J Physiol Cell Physiol, December 1, 2009; 297(6): C1567 - C1575. [Abstract] [Full Text] [PDF] S. Pelucchi, R. Mariani, P. Trombini, S. Coletti, M. Pozzi, V. Paolini, D. Barisani, and A. Piperno Expression of hepcidin and other iron-related genes in type 3 hemochromatosis due to a novel mutation in transferrin receptor-2 Haematologica, February 1, 2009; 94(2): 276 - 279. [Abstract] [Full Text] [PDF] A.-S. Zhang and C. A. Enns Iron Homeostasis: Recently Identified Proteins Provide Insight into Novel Control Mechanisms J. Biol. Chem., January 9, 2009; 284(2): 711 - 715. [Abstract] [Full Text] [PDF] N. C. Andrews Forging a field: the golden age of iron biology Blood, July 15, 2008; 112(2): 219 - 230. [Full Text] [PDF] D. F. Wallace, L. Summerville, E. M. Crampton, and V. N. Subramaniam Defective trafficking and localization of mutated transferrin receptor 2: implications for type 3 hereditary hemochromatosis Am J Physiol Cell Physiol, February 1, 2008; 294(2): C383 - C390. [Abstract] [Full Text] [PDF] E. Camberlein, G. Zanninelli, L. Detivaud, A. R. Lizzi, F. Sorrentino, S. Vacquer, M.-B. Troadec, E. Angelucci, E. Abgueguen, O. Loreal, et al. Anemia in -thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression Haematologica, January 1, 2008; 93(1): 111 - 115. [Abstract] [Full Text] [PDF] J. Chen, M. Chloupkova, J. Gao, T. L. Chapman-Arvedson, and C. A. Enns HFE Modulates Transferrin Receptor 2 Levels in Hepatoma Cells via Interactions That Differ from Transferrin Receptor 1-HFE Interactions J. Biol. Chem., December 21, 2007; 282(51): 36862 - 36870. [Abstract] [Full Text] [PDF] S. Renaud, E. M. Pugacheva, M. D. Delgado, R. Braunschweig, Z. Abdullaev, D. Loukinov, J. Benhattar, and V. Lobanenkov Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors Nucleic Acids Res., December 18, 2007; 35(21): 7372 - 7388. [Abstract] [Full Text] [PDF] T. Goswami and N. C. Andrews Hereditary Hemochromatosis Protein, HFE, Interaction with Transferrin Receptor 2 Suggests a Molecular Mechanism for Mammalian Iron Sensing J. Biol. Chem., September 29, 2006; 281(39): 28494 - 28498. [Abstract] [Full Text] [PDF] S. J. Wilkins, D. M. Frazer, K. N. Millard, G. D. McLaren, and G. J. Anderson Iron metabolism in the hemoglobin-deficit mouse: correlation of diferric transferrin with hepcidin expression Blood, February 15, 2006; 107(4): 1659 - 1664. [Abstract] [Full Text] [PDF]

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