Publications by authors named "Megumi Kumagai"
Article Synopsis
- Compounds that target the circadian clock show promise as treatments for diseases related to the clock, like cancer, with new ones being discovered through phenotypic screening.
- Researchers identified a specific compound, GO289, which effectively lengthens the circadian period and acts as a potent CK2 inhibitor, impacting multiple phosphorylation sites on clock proteins.
- The detailed structure of the CK2α-GO289 complex highlights how GO289 interacts selectively with CK2, providing insights into the relationship between circadian rhythms and cancer, as well as innovative design principles for developing kinase inhibitors.
In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy.
View Article and Find Full Text PDFReal-time analysis of the circadian oscillation of the Rev-Erb β promoter.
J Atheroscler Thromb
September 2013
Aim: Rev-Erb β gene plays crucial roles in circadian rhythm, lipid and glucose metabolism, and several diseases. The molecular mechanisms of the transcriptional regulation of Rev-Erb β that generate and determine the phase of the circadian oscillation remain unclear.
Methods: We analyzed the Rev-Erb β promoter by luciferase reporter assays, real-time bioluminescence monitoring assays and electrophoretic mobility shift assays.
Aim: PPARgamma (peroxisome proliferator-activated receptor gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. Herein, we show that expression levels of the novel PPARgamma transcript exhibit circadian oscillation. To study the mechanisms controlling PPARgamma expression, a novel PPARgamma gene promoter was cloned and characterized.
View Article and Find Full Text PDFThe molecular mechanism regulating the autonomous circadian expression of Topoisomerase I in NIH3T3 cells.
Biochem Biophys Res Commun
February 2009
To identify whether Topoisomerase I (TopoI) has autonomous circadian rhythms regulated by clock genes, we tested mouse TopoI (mTopoI) promoter oscillation in NIH3T3 cells using a real-time monitoring assay and TopoI mRNA oscillations using real-time RT-PCR. Analysis of the mTopoI promoter region with Matlnspector software revealed two putative E-box (E1 and E2) and one DBP/E4BP4-binding element (D-box). Luciferase assays indicated that mTopoI gene expression was directly regulated by clock genes.
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