Period circadian protein 2 (PER2)

Period circadian protein 2 (PER2) is a fundamental component of the mammalian molecular clock, serving as a key negative regulator in the transcription-translation feedback loop (TTFL) that governs 24-hour biological rhythms [UniProt: O15055]. It functions by forming complexes with Cryptochrome (CRY) proteins, which then translocate to the nucleus to inhibit the CLOCK-BMAL1-mediated transcription of clock-controlled genes [PubMed: 11230151]. Beyond its primary role in chronobiology, PER2 is recognized as a potent tumor suppressor that influences cell cycle progression, DNA damage repair, and apoptosis [PubMed: 21629166]. Mutations in the PER2 gene are directly linked to Familial Advanced Sleep Phase Syndrome (FASPS), where individuals exhibit significantly early sleep and wake times [PubMed: 11170517]. In the context of drug development, PER2 is a target for small molecules aimed at treating sleep disorders, metabolic diseases, and certain cancers by modulating its stability or its interaction with kinases like Casein Kinase 1 [PubMed: 22791712]. Pharmacological intervention typically involves stabilizing the protein to delay the circadian phase or enhancing its expression to leverage its anti-oncogenic properties.

Other names

PER2Period 2Circadian clock protein PERIOD 2FASPSFASPS1

Modulation of protein stability through inhibition of Casein Kinase 1 (CK1) mediated phosphorylation or stabilization of the PER-CRY complex to regulate the circadian negative feedback loop.