Abstract |
Iron plays an essential role in cell proliferation and is a required cofactor for a number of critical cellular enzymes. In this report we investigate changes in proteins of iron metabolism during p53-mediated replicative arrest. Following the induction of p53 in H1299 lung cancer cells containing a doxycycline-inducible p53, an increase in both H and L subunits of ferritin protein was observed. To determine the mechanism of this effect, we investigated the ability of p53 to regulate ferritin. Real time reverse transcription-PCR demonstrated no difference in levels of ferritin H mRNA in the presence and absence of p53. Because these results suggested that transcriptional mechanisms were not responsible for the p53-dependent increase in ferritin, we tested whether a post-transcriptional mechanism was involved. RNA bandshift assays revealed that induction of p53 decreased iron regulatory protein binding. Consistent with this observation, Western blot analysis revealed a decline in transferrin receptor 1 protein levels following induction of p53. Collectively, these results suggest that p53 may induce cell cycle arrest not only by well described mechanisms involving the induction of cyclin-dependent kinase inhibitors but also by the recruitment of pathways that reduce the availability of intracellular iron.
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Authors | Fan Zhang, Wei Wang, Yoshiaki Tsuji, Suzy V Torti, Frank M Torti |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 283
Issue 49
Pg. 33911-8
(Dec 05 2008)
ISSN: 0021-9258 [Print] United States |
PMID | 18819919
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, CD
- CD71 antigen
- Cation Transport Proteins
- Receptors, Transferrin
- TP53 protein, human
- Tumor Suppressor Protein p53
- metal transporting protein 1
- Ferritins
- Apoferritins
- Iron
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Topics |
- Antigens, CD
(chemistry)
- Apoferritins
(chemistry)
- Cation Transport Proteins
(biosynthesis, chemistry)
- Cell Cycle
- Cell Line, Tumor
- Ferritins
(chemistry)
- Homeostasis
- Humans
- Iron
(chemistry)
- Models, Biological
- Protein Binding
- Protein Structure, Tertiary
- RNA Processing, Post-Transcriptional
- Receptors, Transferrin
(chemistry)
- Transcription, Genetic
- Tumor Suppressor Protein p53
(metabolism)
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