The human PER1 gene is transcriptionally regulated by multiple signaling pathways

The mammalian period ( Per) genes are components of the circadian clock and appear to be regulated via an autoregulatory feedback loop. Here we show that the human PER1 ( hPER1) gene is synergistically activated by protein kinases A and C (PKA, PKC) and cAMP responsive element binding protein. Activ...

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Veröffentlicht in:	FEBS letters 2000-12, Vol.486 (3), p.315-319
Hauptverfasser:	Motzkus, Dirk, Maronde, Erik, Grunenberg, Uwe, Lee, Cheng Chi, Forssmann, Wolf-Georg, Albrecht, Urs
Format:	Artikel
Sprache:	eng
Schlagworte:	Cell Cycle Proteins Cell Line Chronobiology Circadian rhythm Circadian Rhythm - genetics Clock resetting Colforsin - pharmacology CREB, cAMP responsive element binding protein Cyclic AMP - analogs & derivatives Cyclic AMP - pharmacology Cyclic AMP Response Element-Binding Protein - genetics Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - metabolism Cyclic AMP-Dependent Protein Kinases - pharmacology Dichlororibofuranosylbenzimidazole - analogs & derivatives Dichlororibofuranosylbenzimidazole - pharmacology Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Genes, Regulator - drug effects Genes, Regulator - genetics Genes, Reporter Human Per gene Humans Nuclear Proteins - genetics PBGD, porphobilinogen deaminase Period Circadian Proteins PKA, protein kinase A PKC, protein kinase C PMA, phorbol 12-myristate 13-acetate Polymerase Chain Reaction Promoter Regions, Genetic - genetics Protein Kinase C - antagonists & inhibitors Protein Kinase C - metabolism Protein Kinase C - pharmacology RNA, Messenger - metabolism Rp-8-CPT-cAMPS, 8-(4-chlorophenylthio)adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer Signal Transduction - genetics Signaling pathway Sp-5,6-DCl-cBiMPS, 5,6-dichlorobenzimidazole-1-β-D-ribofuranosyl-3′,5′-monophosphorothioate, Sp-isomer Thionucleotides - pharmacology Transfection
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Zusammenfassung:	The mammalian period ( Per) genes are components of the circadian clock and appear to be regulated via an autoregulatory feedback loop. Here we show that the human PER1 ( hPER1) gene is synergistically activated by protein kinases A and C (PKA, PKC) and cAMP responsive element binding protein. Activators and inhibitors of PKA as well as PKC modulate endogenous hPER1 expression and hPER1 promoter-driven reporter gene activity in a dose-dependent manner. Our results suggest that the hPER1 promoter acts as a sensor for multiple signaling molecules thereby integrating different physiological parameters. This regulation of hPER1 appears to be significant for rapid adaptation to changing environmental conditions.
ISSN:	0014-5793 1873-3468
DOI:	10.1016/S0014-5793(00)02315-2