Research Project
Grant-in-Aid for Challenging Exploratory Research
Iron is an important biological catalyst and is critical for DNA synthesis during cell proliferation. Cellular iron uptake is enhanced in tumor cells to support increased DNA synthesis. In this study, we identified a 24-hr rhythm in iron levels in colon-26 tumors implanted in mice and the expression of iron regulatory protein 2 (IRP2). Furthermore, IRP2 regulated the 24-hr rhythm of transferrin receptor 1 (TfR1) mRNA expression post-transcriptionally by binding to RNA stem-loop structures known as iron-response elements. The transcription of IRP2 mRNA was promoted by circadian clock genes, including BMAL1 and CLOCK heterodimer. The expression of IRP2 in tumor cells was affected by the circadian organization of the molecular clock. Our findings suggest that circadian organization contributes to cell proliferation by regulating iron metabolism and may play a role in the circadian rhythm of other metals.
All 2015 2014 2013
All Journal Article (5 results) (of which Peer Reviewed: 5 results, Open Access: 3 results, Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Invited: 2 results)
Mol Pharmacol
Volume: 87 Issue: 2 Pages: 314-322
10.1124/mol.114.094979
J Biol Chem.
Volume: 289(36) Issue: 36 Pages: 25296-25305
10.1074/jbc.m114.577023
Joumal of lnvestigative Dermatology
Volume: (印刷中) Issue: 6 Pages: 1636-1644
10.1038/jid.2014.13
Volume: 85 Issue: 5 Pages: 715-722
10.1124/mol.113.089805
Cancer Res.
Volume: 74 Issue: 2 Pages: 543-551
10.1158/0008-5472.can-12-3241