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Blood, 1 May 2007, Vol. 109, No. 9, pp. 4045-4054. Prepublished online as a Blood First Edition Paper on December 29, 2006; DOI 10.1182/blood-2006-10-047753. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-10-047753v1 109/9/4045    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Nurtjahja-Tjendraputra, E. Articles by Richardson, D. R. Search for Related Content PubMed PubMed Citation Articles by Nurtjahja-Tjendraputra, E. Articles by Richardson, D. R. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency–mediated growth suppression Effie Nurtjahja-Tjendraputra1,2, Dong Fu2, Juanita M. Phang1, and Des R. Richardson1,2 1 Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, New South Wales, Australia; 2 Iron Metabolism and Chelation Program, Children's Cancer Institute Australia for Medical Research, Sydney, New South Wales, Australia Iron (Fe) plays an important role in proliferation, and Fe deficiency results in G1/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G1 progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marked decrease in cyclin D1 protein, although the mechanism involved was unknown. In this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1 protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1 half-life in control cells was 80 ± 15 minutes (n = 5), while in chelator-treated cells it was significantly (P < .008) decreased to 38 ± 3 minutes (n = 5). Proteasomal inhibitors rescued the Fe chelator–mediated decrease in cyclin D1 protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1 was degraded in an ubiquitin-dependent manner, while Fe depletion induced a ubiquitin-independent pathway. This is the first report linking Fe depletion–mediated growth suppression at G1/S to a mechanism inducing cyclin D1 proteolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Amit, Y. Avramovich-Tirosh, M. B. H. Youdim, and S. Mandel Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators FASEB J, May 1, 2008; 22(5): 1296 - 1305. [Abstract] [Full Text] [PDF] M. Neri, C. Maderna, C. Cavazzin, V. Deidda-Vigoriti, L. S. Politi, G. Scotti, P. Marzola, A. Sbarbati, A. L. Vescovi, and A. Gritti Efficient In Vitro Labeling of Human Neural Precursor Cells with Superparamagnetic Iron Oxide Particles: Relevance for In Vivo Cell Tracking Stem Cells, February 1, 2008; 26(2): 505 - 516. [Abstract] [Full Text] [PDF] D. Fu and D. R. Richardson Iron chelation and regulation of the cell cycle: 2 mechanisms of posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion Blood, July 15, 2007; 110(2): 752 - 761. [Abstract] [Full Text] [PDF]

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