The human PER1 gene is transcriptionally regulated by multiple signaling pathways

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Circadian rhythm;Chronobiology;Human Per gene;Signaling pathway;Clock resetting;CREB;cAMP responsive element binding protein;PBGD;porphobilinogen deaminase;PKA;protein kinase A;PKC;protein kinase C;PMA;phorbol 12-myristate 13-acetate;Rp-8-CPT-cAMPS;8-(4-chlorophenylthio)adenosine-3′;5′-cyclic monophosphorothioate;Rp-isomer;Sp-5;6-DCl-cBiMPS;5;6-dichlorobenzimidazole-1-β-D-ribofuranosyl-3′;5′-monophosphorothioate;Sp-isomer