Period circadian regulator 1 (PER1)

Period circadian regulator 1 (PER1) is a core transcriptional regulator of the mammalian circadian clock, orchestrating cell autonomous 24-hour oscillations in gene expression, especially in the suprachiasmatic nucleus and peripheral tissues. PER1 protein functions in a feedback loop: activated by the CLOCK/BMAL1 complex, it heterodimerizes with CRY proteins and translocates to the nucleus, where it inhibits its own transcription and other clock gene expression, ensuring rhythmic cycles. Post-translational modifications, like CK1ε/δ phosphorylation and ubiquitin-mediated proteasomal degradation, fine-tune its abundance and timing. PER1 is implicated as a tumor suppressor, with loss or downregulation associated with proliferation, impaired apoptosis, altered DNA repair, and therapy resistance in various cancers. Additional roles include mediating metabolic responses to toxins, modulating glucocorticoid signaling, and influencing neurobehavioral phenotypes through clock gene regulation.

Other names

Period circadian protein homolog 1Period circadian clock 1Period homolog 1KIAA0482RIGUIhPER1Circadian clock protein PERIOD 1Circadian pacemaker protein RiguiCircadian pacemaker protein RIGUI

Mechanism of action for drugs targeting PER1 would involve chronotherapeutics (modulation of PER1 expression or function to restore normal circadian gene expression cycles, enhance apoptosis, and suppress tumor growth). This can include epigenetic modulation (altering promoter methylation to restore PER1 expression, especially in cancer), protein-protein interaction disruption (targeting feedback inhibition mechanisms, e.g., PER/CRY interaction with CLOCK-BMAL1), or modulation of metabolic regulators (e.g., interaction with HNF-1α to regulate CYP2E1-mediated toxin metabolism).