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| CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression |
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| Author(s): Maemura K, de la Monte SM, Chin MT, Layne MD, Hsieh CM, Yet SF, Perrella MA, Lee ME |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 275 Issue: 47 Pages: 36847-36851 Published: NOV 24 2000 |
| Times Cited: 100 References: 35 |
| Abstract: The onset of myocardial infarction occurs frequently in the early morning, and it may partly result from circadian variation of fibrinolytic activity. Plasminogen activator inhibitor-1 activity shows a circadian oscillation and may account for the morning onset of myocardial infarction, However, the molecular mechanisms regulating this circadian oscillation remain unknown. Recent evidence indicates that basic helix-loop-helix (bHLH)/PAS domain transcription factors play a crucial role in controlling the biological clock that controls circadian rhythm. We isolated a novel bHLH/PAS protein, cycle-like factor (CLIF) rom human umbilical vein endothelial cells. CLIF shares high homology with Drosophila CYCLE, one of the essential transcriptional regulators of circadian rhythm. CLIF is expressed in endothelial cells and neurons in the brain, including the suprachiasmatic nucleus, the center of the circadian clock, In endothelial cells, CLIF forms a heterodimer with CLOCK and up-regulates the PAI-1 gene through E-box sites. Furthermore, Period2 and Cryptochrome1, whose expression show a circadian oscillation in peripheral tissues, inhibit the PAI-1 promoter activation by the CLOCK:CLIF heterodimer. These results suggest that CLIF regulates the circadian oscillation of PAI-1 gene expression in endothelial cells. In addition, the results potentially provide a molecular basis for the morning onset of myocardial infarction, |
| Document Type: Article |
| Language: English |
| Reprint Address: Maemura, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo 1138655, Japan |
Addresses:
1. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA
2. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02115 USA
3. Brown Univ, Rhode Isl Hosp, Sch Med, Dept Pathol & Med, Providence, RI 02903 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 378GY |
| ISSN: 0021-9258 |
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