|
|
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.
 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:
|
|
|
|
 
L. Kupershmidt, O. Weinreb, T. Amit, S. Mandel, M. T. Carri, and M. B. H. Youdim
Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis
FASEB J,
November 1, 2009;
23(11):
3766 - 3779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Assinder, Q. Dong, H. Mangs, and D. R. Richardson
Pharmacological Targeting of the Integrated Protein Kinase B, Phosphatase and Tensin Homolog Deleted on Chromosome 10, and Transforming Growth Factor-{beta} Pathways in Prostate Cancer
Mol. Pharmacol.,
March 1, 2009;
75(3):
429 - 436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. A. Rao, S. R. Klein, K. K. Agama, E. Toyoda, N. Adachi, Y. Pommier, and E. B. Shacter
The Iron Chelator Dp44mT Causes DNA Damage and Selective Inhibition of Topoisomerase II{alpha} in Breast Cancer Cells
Cancer Res.,
February 1, 2009;
69(3):
948 - 957.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zhang, W. Wang, Y. Tsuji, S. V. Torti, and F. M. Torti
Post-transcriptional Modulation of Iron Homeostasis during p53-dependent Growth Arrest
J. Biol. Chem.,
December 5, 2008;
283(49):
33911 - 33918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
