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      Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop.

      Science (New York, N.Y.)

      metabolism, Acetylcysteine, Ubiquitin, Transfection, Transcription, Genetic, Rats, genetics, biosynthesis, RNA, Messenger, pharmacology, Protein Synthesis Inhibitors, Protein Biosynthesis, Proteasome Endopeptidase Complex, Protease Inhibitors, Periodicity, PC12 Cells, Multienzyme Complexes, Mice, Mesoderm, Leupeptins, Homeodomain Proteins, Half-Life, Glycosyltransferases, Gene Expression Regulation, Feedback, Physiological, Cysteine Endopeptidases, Cycloheximide, Cell Line, Blood, Biological Clocks, Basic Helix-Loop-Helix Transcription Factors, Animals, analogs & derivatives

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          Abstract

          Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome-mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.

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          Journal
          12399594
          10.1126/science.1074560

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