Affinage

PER1

Period circadian protein homolog 1 · UniProt O15534

Length
1290 aa
Mass
136.2 kDa
Annotated
2026-04-29
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PER1 is a core component of the mammalian circadian clock that functions both as a transcriptional co-regulator within the negative feedback loop and as a versatile protein–protein interaction hub linking circadian timing to metabolism, hormone signaling, hypoxia, and tumor suppression. Identified as the mammalian ortholog of Drosophila period, PER1 is rhythmically expressed in the suprachiasmatic nucleus and peripheral tissues, is transcriptionally activated by CLOCK/BMAL1 via E-box elements and additional regulators including EGR1, progesterone receptor, and the PER2-dependent CREB/CRTC1/CBP complex, and is post-transcriptionally regulated by IRE1α-mediated mRNA decay and miR-34a targeting (PMID:9323128, PMID:24062694, PMID:26471974, PMID:31518992, PMID:34741086, PMID:23752693, PMID:26923637). At the effector level, PER1 occupies E-box-containing promoters together with CLOCK to drive circadian transcription of renal sodium transport genes (αENaC, NHE3, SGLT1), forms complexes with PPARγ to regulate glycolytic gene oscillation, promotes HIF-1α protein degradation, inhibits androgen receptor transactivation, and reduces p53 stability, thereby influencing cell proliferation, apoptosis, ferroptosis, and drug resistance (PMID:26377793, PMID:35255118, PMID:35134674, PMID:19752089, PMID:33804124). Beyond its canonical circadian role, local Per1 expression in the dorsal hippocampus is required for spatial memory consolidation independent of SCN-driven rhythms (PMID:37264172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    The identification of PER1 (RIGUI) as a bHLH/PAS-domain mammalian ortholog of Drosophila period, with circadian expression in the SCN persisting in constant darkness, established for the first time that mammals possess a molecular clock gene homologous to invertebrate period.

    Evidence Molecular cloning, sequence homology, in situ hybridization and Northern blotting under constant darkness and shifted LD cycles in mouse SCN

    PMID:9323128

    Open questions at the time
    • No loss-of-function data to confirm requirement for circadian rhythmicity
    • Protein-level rhythmicity not demonstrated
    • No mechanistic insight into how PER1 feeds back on the clock
  2. 1999 High

    Demonstrating that Per1 mRNA amplitude in the pars tuberalis encodes photoperiodic time established PER1 as a decoder of melatonin signal duration, extending its role from circadian oscillator to seasonal timer.

    Evidence In situ hybridization of Per1 in Syrian hamster pars tuberalis under long vs. short photoperiods with melatonin signal manipulation

    PMID:10449798

    Open questions at the time
    • Mechanism by which melatonin controls Per1 transcription in PT not defined
    • Downstream effectors of Per1 amplitude in seasonal physiology unknown
  3. 2001 Medium

    Discovery of tissue-specific PER1 isoforms and its physical interaction with HIF-1α revealed cross-talk between circadian PAS-domain proteins and the hypoxia response, though functional consequences were unclear.

    Evidence Immunoblotting of nuclear/cytoplasmic fractions across tissues, co-immunoprecipitation of PER1 and HIF-1α

    PMID:11726537

    Open questions at the time
    • Only forward co-IP shown; reciprocal validation absent in original study
    • Functional impact of PER1–HIF-1α interaction on either pathway not demonstrated
    • Isoform-specific functions unresolved
  4. 2007 Medium

    Showing that estradiol and progesterone regulate Per1 expression in distinct uterine compartments via their cognate receptors established hormonal control of Per1 as a mechanism coupling reproductive steroid signaling to local peripheral clocks.

    Evidence In situ hybridization and RT-PCR in ovariectomized rats with receptor antagonist (ICI182780, RU486) blockade

    PMID:17761890

    Open questions at the time
    • Whether steroid hormones directly bind the Per1 promoter or act indirectly was not resolved
    • Functional consequence of Per1 induction for uterine physiology not tested
  5. 2009 Medium

    PER1's physical interaction with the androgen receptor and inhibition of AR transactivation, causing growth arrest and apoptosis in prostate cancer cells, revealed a direct molecular link between the circadian clock protein and hormone-dependent cancer.

    Evidence Co-IP of PER1–AR, reporter assays for AR transactivation, siRNA/overexpression with proliferation and apoptosis readouts in LNCaP cells

    PMID:19752089

    Open questions at the time
    • Domain mapping of PER1–AR interaction not performed
    • Mechanism of growth inhibition downstream of AR repression not delineated
    • In vivo confirmation with genetic models absent
  6. 2013 High

    Two parallel discoveries established PER1 as an output transcription factor of the renal clock and as a target of IRE1α-mediated post-transcriptional regulation: PER1 and MR co-regulate αENaC transcription via E-box elements, while IRE1α endonuclease degrades PER1 mRNA post-transcriptionally in tumor cells, providing a mechanism for circadian disruption in cancer.

    Evidence ChIP, E-box mutagenesis, and reporter assays for αENaC regulation; siRNA, dominant-negative IRE1α, and hnRNA assays for post-transcriptional decay

    PMID:23752693 PMID:24062694

    Open questions at the time
    • Whether IRE1α cleaves PER1 mRNA directly or via an intermediate is unresolved
    • αENaC regulation not tested in Per1-null animals
  7. 2015 High

    Extension of PER1's renal transcriptional targets to NHE3 and SGLT1 — with ChIP confirming PER1 and CLOCK co-occupancy at these promoters — consolidated PER1 as a direct circadian transcriptional regulator of renal sodium transport, and EGR1 was identified as an intermediate transcription factor linking CLOCK/BMAL1 to Per1 promoter activation.

    Evidence ChIP, siRNA, pharmacological nuclear entry blockade, hnRNA analysis for renal targets; ChIP, reporter assays, and Egr1-KO mice for EGR1–Per1 axis

    PMID:26377793 PMID:26471974

    Open questions at the time
    • Whether EGR1-mediated Per1 regulation occurs in non-hepatic tissues unknown
    • Relative contribution of E-box vs. EGR1-binding site to Per1 amplitude not quantified
  8. 2016 Medium

    Identification of PER1 as a direct target of miR-34a added a microRNA layer to post-transcriptional clock control and showed that Per1 overexpression suppresses cholangiocarcinoma growth, reinforcing its tumor-suppressive function.

    Evidence Luciferase reporter assay for 3′UTR targeting, miR-34a modulation with in vivo tumor xenograft readouts

    PMID:26923637

    Open questions at the time
    • Whether miR-34a regulation of PER1 is circadian phase-dependent not tested
    • Downstream effectors of PER1-mediated growth suppression in cholangiocarcinoma uncharacterized
  9. 2019 High

    Progesterone receptor directly binds the PER1 promoter to activate its transcription during endometrial decidualization, and PER1 knockout impairs decidualization by destabilizing FOXO1, revealing a specific reproductive function downstream of PER1.

    Evidence ChIP for PR at PER1 promoter, PER1 knockout in stromal cells with FOXO1 protein stability and decidualization assays

    PMID:31518992

    Open questions at the time
    • Whether FOXO1 stabilization is a direct PER1 protein interaction or transcriptional effect not resolved
    • Relevance to in vivo fertility phenotypes not demonstrated
  10. 2021 High

    Two studies deepened PER1's role in transcription factor regulation: PER2 was shown to scaffold CREB/CRTC1/CBP assembly at the Per1 CRE element for light-induced Per1 transcription, and PER1 was found to physically interact with p53, reducing its stability and transcriptional activity, with functional consequences for drug-induced apoptosis.

    Evidence Co-IP, ChIP, histone acetylation, and RNA Pol II ChIP in Per2-KO SCN tissue; co-IP, reporter assays, overexpression/knockdown with xenograft models for PER1–p53

    PMID:33804124 PMID:34741086

    Open questions at the time
    • Whether PER1 promotes p53 degradation via ubiquitin-proteasome pathway not established
    • Domain requirements for PER1–p53 interaction unknown
    • PER2-mediated Per1 induction mechanism not shown to be conserved in peripheral tissues
  11. 2022 Medium

    A cluster of 2022 studies established PER1 as (i) a PPARγ co-factor driving circadian HK2 oscillation and glycolytic drug resistance, (ii) a direct promoter of HIF-1α degradation forming a reciprocal negative feedback loop that controls ferroptosis, (iii) a target of KLF9-mediated transcriptional activation via a lncRNA sponge pathway in gastric cancer, and (iv) a regulator of testosterone biosynthesis through the PKA-CREB-StAR axis.

    Evidence Co-IP, siRNA, glycolysis assays, chronotherapy experiments for PPARγ–PER1; co-IP, CHX chase, ChIP, dual luciferase for PER1–HIF-1α loop; ChIP for KLF9 at PER1 promoter and xenograft assays; Per1/Per2 double-KO mice with hormone metabolomics and PKA-StAR pathway analysis

    PMID:35134674 PMID:35255118 PMID:35806403 PMID:35985238

    Open questions at the time
    • PPARγ–PER1 complex composition and DNA-binding mode unresolved
    • Whether PER1 recruits a specific E3 ligase for HIF-1α degradation is unknown
    • Per1 vs. Per2 individual contributions to steroidogenesis not separated in double-KO
  12. 2023 Medium

    Local knockdown of Per1 in dorsal hippocampus impaired spatial memory consolidation without affecting circadian rhythm or sleep, establishing a non-canonical, circuit-level function for PER1 outside the SCN clock network.

    Evidence Lentiviral Per1 knockdown in dorsal hippocampus with Object Location Memory testing and RNA-seq

    PMID:37264172

    Open questions at the time
    • Molecular targets of PER1 in hippocampal memory consolidation not identified
    • Whether other Period genes compensate or share this function unknown
    • Electrophysiological correlates of Per1-dependent memory consolidation not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of PER1's interaction with its diverse protein partners (AR, HIF-1α, p53, PPARγ), whether PER1 recruits specific ubiquitin ligases for target degradation, how tissue-specific isoforms (48 vs. 55 kDa) differ functionally, and the full scope of PER1's non-circadian roles in memory and reproduction.
  • No crystal or cryo-EM structure of PER1 in complex with any partner
  • Isoform-specific functions remain entirely uncharacterized
  • No genome-wide PER1 ChIP-seq in peripheral tissues to define direct target gene repertoire

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-9909396 Circadian clock 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 4 R-HSA-1474165 Reproduction 2 R-HSA-382551 Transport of small molecules 2
Partners
ARCLOCKEGR1HIF1ANR3C2PGRPPARGTP53
Complex memberships
PER1–CLOCK transcriptional complexPER1–PPARγ transcriptional complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 RIGUI/PER1 encodes a bHLH/PAS protein 44% homologous to Drosophila period, and is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN); expression continues in constant darkness and shifts proportionally with light/dark cycle changes, establishing PER1 as a mammalian ortholog of the Drosophila period gene. Molecular cloning, sequence homology analysis, in situ hybridization/Northern blotting under constant darkness and shifted light/dark cycles Cell High 9323128
2001 PER1 protein exists in multiple tissue-specific isoforms (48 kDa nuclear form in brain, 55 kDa in kidney); a nuclear 48 kDa isoform follows a daily rhythm in mouse brain. Hypoxia increases PER1 protein levels and PER1 physically interacts with HIF-1α via co-immunoprecipitation, suggesting cross-talk between circadian and hypoxic PAS-domain pathways. Immunoblotting of nuclear/cytoplasmic fractions, co-immunoprecipitation, tissue fractionation FASEB journal Medium 11726537
1999 Per1 mRNA amplitude in the pars tuberalis (PT) encodes photoperiodic time: the duration of the nocturnal melatonin signal is decoded as amplitude of Per1 (and ICER) gene expression in the PT, with short photoperiods greatly attenuating the peak. In situ hybridization of Per1 expression under long and short photoperiods in Syrian hamsters, manipulation of melatonin signal duration PNAS High 10449798
2009 PER1 physically interacts with the androgen receptor (AR) and inhibits AR transactivation; forced expression of PER1 in LNCaP prostate cancer cells diminishes expression of androgen-sensitive genes and causes growth inhibition and apoptosis. Co-immunoprecipitation, reporter assays (transactivation), siRNA/overexpression with proliferation and apoptosis readouts Cancer research Medium 19752089
2013 IRE1α endoribonuclease activity degrades PER1 mRNA post-transcriptionally in tumor cells without affecting PER1 gene transcription; inhibition of IRE1α prevents PER1 mRNA decay and reduces tumorigenesis. siRNA-mediated silencing, dominant-negative IRE1α strategy, qRT-PCR for mRNA vs. hnRNA, tumor growth assays Cancer research High 23752693
2013 Per1 and the mineralocorticoid receptor (MR) coordinately regulate αENaC transcription through E-box elements in the αENaC promoter; aldosterone increases Per1 occupancy on the αENaC E-box, and mutation of these E-boxes abolishes both basal and aldosterone-mediated promoter activity. Site-directed mutagenesis of E-boxes, DNA pull-down assays, chromatin immunoprecipitation (ChIP), reporter assays Frontiers in physiology High 24062694
2014 Per1 regulates expression of the endothelin axis genes (ET-1, ETA, ETB) in a tissue-specific and time-dependent manner in mouse kidney, lung, liver, and heart. Quantitative RT-PCR in Per1 heterozygous vs. wild-type mice tissues collected at rest and active phases Life sciences Medium 24721511
2015 Per1 transcriptionally regulates NHE3 and SGLT1 (but not SGLT2) in renal proximal tubule cells; Per1 and CLOCK are detected at the NHE3 and SGLT1 promoters by ChIP, and pharmacological blockade of nuclear Per1 entry or siRNA knockdown decreases both mRNA and protein levels of NHE3 and SGLT1 and reduces Na⁺-K⁺-ATPase activity. ChIP, siRNA knockdown, pharmacological nuclear entry blockade, heterogeneous nuclear RNA analysis, protein immunoblotting American journal of physiology. Renal physiology High 26377793
2015 EGR1 directly binds the proximal Per1 promoter to activate Per1 transcription; CLOCK/BMAL1 heterodimer transactivates Egr1 via a conserved E-box, placing EGR1 as an intermediate regulator of Per1 amplitude in the hepatic clock. Chromatin immunoprecipitation, luciferase reporter assays, Egr1-deficient mouse model with hepatic clock gene expression analysis Scientific reports High 26471974
2019 The progesterone receptor (PR) directly binds the PER1 promoter to activate PER1 transcription during human endometrial decidualization; PER1 knockout attenuates decidual transformation by accelerating FOXO1 protein degradation. ChIP assay for PR at PER1 promoter, PER1 knockout in stromal cells, FOXO1 protein stability assays, qRT-PCR The Journal of endocrinology High 31518992
2021 PER2 acts as a co-factor of CREB to facilitate formation of a transactivation complex (CREB/CRTC1/CBP) on the CRE element of the Per1 gene promoter in response to light or forskolin; absence of PER2 abolishes CBP-CREB interaction, reduces histone H3 acetylation, and decreases RNA Pol II recruitment to the Per1 gene. Co-immunoprecipitation, ChIP, in vitro and in vivo approaches with Per2 knockout, histone acetylation assays, RNA Pol II ChIP Scientific reports High 34741086
2021 PER1 physically interacts with p53, reducing p53 stability and impairing its transcriptional activity; conversely, p53 represses PER1 transcription. PER1 overexpression reduces cancer cell sensitivity to drug-induced apoptosis in vitro and in vivo in xenograft models. Co-immunoprecipitation, reporter assays, overexpression/knockdown with apoptosis readouts, xenograft mouse model International journal of molecular sciences Medium 33804124
2022 PER1 forms a transcriptional complex with PPARγ to regulate circadian oscillation of HK2 expression; silencing PER1 disrupts the circadian rhythm of HK2-dependent glycolysis and reverses trastuzumab resistance in gastric cancer cells. Co-immunoprecipitation, siRNA knockdown, in vitro and in vivo glycolysis assays, chronotherapy experiments Cancer research Medium 35255118
2022 PER1 binds to HIF-1α protein to promote HIF-1α protein degradation (shown by co-immunoprecipitation and cycloheximide chase); HIF-1α in turn binds the PER1 promoter to feedback-inhibit PER1 transcription (shown by ChIP and dual luciferase assay), forming a PER1/HIF-1α negative feedback loop that promotes ferroptosis in oral squamous cell carcinoma. Co-immunoprecipitation, cycloheximide chase assay, ChIP, dual luciferase reporter assay, in vivo tumorigenicity assays Translational oncology High 35134674
2016 miR-34a directly targets PER1 mRNA to inhibit its expression; decreased miR-34a leads to increased Per1 levels that suppress cholangiocarcinoma cell proliferation and tumor growth; mRNA profiling shows Per1 overexpression regulates cell cycle, growth, and apoptosis pathways. Luciferase reporter assay for miRNA targeting, miR-34a inhibition/overexpression, cell proliferation and apoptosis assays, in vivo tumor growth, mRNA profiling Journal of hepatology Medium 26923637
2022 LncRNA TPTEP1 sponges miR-548d-3p to derepress KLF9, which binds the PER1 promoter to activate PER1 transcription, thereby inhibiting gastric cancer cell migration and invasion. Luciferase assay for sponge activity and 3'UTR targeting, ChIP for KLF9 binding to PER1 promoter, wound healing and transwell assays, nude mouse xenograft Pathology, research and practice Medium 35985238
2022 Per1/Per2 double knockout in mice reduces testosterone synthesis by downregulating steroidogenic enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, StAR) via impaired PKA-CREB-StAR signaling, leading to decreased sperm motility and reduced fertility in elderly males. Per1/Per2 double knockout mouse model, hormone-targeted metabolomics, transcriptomic analysis, Western blotting for StAR, p-CREB, PKA, AC1 International journal of molecular sciences Medium 35806403
2023 Local knockdown of Per1 within the dorsal hippocampus impairs spatial memory consolidation without affecting circadian rhythm or sleep, demonstrating a local, circuit-level role for Per1 in hippocampal memory independent of its SCN circadian function. Lentiviral Per1 knockdown in dorsal hippocampus, Object Location Memory behavioral testing, RNA-sequencing for identification of Per1 as learning-induced oscillator Neuropsychopharmacology Medium 37264172
2015 In the SCN, PER1-expressing neurons are differentially distributed from PER2-expressing neurons across the rostro-caudal extent, with high PER1 expression concentrated in a broad central area and high PER2 in rostral and caudal portions, suggesting spatially distinct functional roles in circadian timekeeping. Triple immunofluorescence labeling and automated image analysis of PER1, PER2, and gastrin-releasing peptide in sagittal SCN sections The European journal of neuroscience Medium 27740710
2007 Estradiol and progesterone upregulate Per1 expression in specific compartments of the rat uterus (LE, GE, M for estradiol; LE, GE, S for progesterone); effects are blocked by the respective receptor antagonists ICI182780 and RU486, demonstrating steroid hormone regulation of Per1 expression. In situ hybridization, immunofluorescence, RT-PCR in ovariectomized rats and cultured uterine stromal cells with hormone/antagonist treatment The Journal of endocrinology Medium 17761890

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 558 9323128
2005 Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 311 15790588
2018 A short review on human exposure to and tissue distribution of per- and polyfluoroalkyl substances (PFASs). The Science of the total environment 282 29913568
1995 A model for circadian oscillations in the Drosophila period protein (PER). Proceedings. Biological sciences 269 8587874
2023 Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS). Environmental health : a global access science source 179 36814257
2009 A role for the clock gene per1 in prostate cancer. Cancer research 159 19752089
2021 Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma. Journal of the National Cancer Institute 156 32944748
1999 Decoding photoperiodic time through Per1 and ICER gene amplitude. Proceedings of the National Academy of Sciences of the United States of America 150 10449798
2023 Insight into the binding model of per- and polyfluoroalkyl substances to proteins and membranes. Environment international 135 37126916
2002 Gradients in the circadian expression of Per1 and Per2 genes in the rat suprachiasmatic nucleus. The European journal of neuroscience 127 11982626
2020 Uptake and accumulation of per- and polyfluoroalkyl substances in plants. Chemosphere 118 32717507
2001 Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 105 11726537
2022 Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes. Chemical research in toxicology 102 35921496
2021 Exposure routes, bioaccumulation and toxic effects of per- and polyfluoroalkyl substances (PFASs) on plants: A critical review. Environment international 101 34592655
2021 Epigenetic changes by per- and polyfluoroalkyl substances (PFAS). Environmental pollution (Barking, Essex : 1987) 100 33751946
2021 Bioactivity profiling of per- and polyfluoroalkyl substances (PFAS) identifies potential toxicity pathways related to molecular structure. Toxicology 99 33887376
2005 Abnormal expression of period 1 (PER1) in endometrial carcinoma. The Journal of pathology 99 15809976
2013 Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα. Cancer research 97 23752693
2022 Per- and Polyfluoroalkyl Substances (PFASs) Impair Lipid Metabolism in Rana nigromaculata: A Field Investigation and Laboratory Study. Environmental science & technology 96 36044002
2021 A Review of Per- and Polyfluorinated Alkyl Substance Impairment of Reproduction. Frontiers in toxicology 86 35295153
2003 High-level expression of recombinant IgG in the human cell line per.c6. Biotechnology progress 86 12573020
2020 Per- and Polyfluoroalkyl Substances in Dust Collected from Residential Homes and Fire Stations in North America. Environmental science & technology 81 33143410
2016 miR-34a-dependent overexpression of Per1 decreases cholangiocarcinoma growth. Journal of hepatology 81 26923637
2022 Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer. Cancer research 80 35255118
2009 Mucilaginibacter rigui sp. nov., isolated from wetland freshwater, and emended description of the genus Mucilaginibacter. International journal of systematic and evolutionary microbiology 80 19648338
2023 Occurrence and Bioaccumulation Patterns of Per- and Polyfluoroalkyl Substances (PFAS) in the Marine Environment. ACS ES&T water 79 37261084
2023 Metabolic Signatures of Youth Exposure to Mixtures of Per- and Polyfluoroalkyl Substances: A Multi-Cohort Study. Environmental health perspectives 78 36821578
2022 Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with oxidative stress biomarkers during pregnancy. Environment international 74 36191484
2016 The Evolution of Per-cell Organelle Number. Frontiers in cell and developmental biology 74 27588285
1995 Transferable production of PER-1 beta-lactamase in Pseudomonas aeruginosa. The Journal of antimicrobial chemotherapy 70 7759392
2010 Deregulated expression of the Per1 and Per2 in human gliomas. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 67 20481271
2019 Per-Nucleus Crossover Covariation and Implications for Evolution. Cell 64 30879787
2020 Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion In Vitro. Toxicological sciences : an official journal of the Society of Toxicology 61 32219433
2016 Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: Implication to exposure pathway. The Science of the total environment 61 26933964
2013 The circadian Per1 and Per2 genes influence alcohol intake, reinforcement, and blood alcohol levels. Behavioural brain research 57 23608482
2014 PDF and cAMP enhance PER stability in Drosophila clock neurons. Proceedings of the National Academy of Sciences of the United States of America 56 24707054
2015 Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells. American journal of physiology. Renal physiology 55 26377793
2007 Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus. The Journal of endocrinology 53 17761890
2020 Per- and Polyfluoroalkyl Substances (PFAS) in Fish from European Lakes: Current Contamination Status, Sources, and Perspectives for Monitoring. Environmental toxicology and chemistry 52 32644251
2023 Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae. Environment international 51 37244004
2021 Tumorigenic activity of alternative per- and polyfluoroalkyl substances (PFAS): Mechanistic in vitro studies. The Science of the total environment 48 34843762
2022 The PER1/HIF-1alpha negative feedback loop promotes ferroptosis and inhibits tumor progression in oral squamous cell carcinoma. Translational oncology 46 35134674
2023 Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment. Chemical research in toxicology 45 37184865
2022 Distribution of per- and poly-fluoroalkyl substances and their precursors in human blood. Journal of hazardous materials 45 36115093
2020 Challenges of aqueous per- and polyfluoroalkyl substances (PFASs) and their foreseeable removal strategies. Chemosphere 45 32120153
2019 Cord blood Per- and polyfluoroalkyl substances, placental steroidogenic enzyme, and cord blood reproductive hormone. Environment international 43 31174145
2015 Circadian genes Per1 and Per2 increase radiosensitivity of glioma in vivo. Oncotarget 43 25760074
2021 Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure. Toxics 41 34062743
2021 Binding of Per- and Polyfluoro-alkyl Substances to Peroxisome Proliferator-Activated Receptor Gamma. ACS omega 41 34151090
2022 Comparative cytotoxicity of seven per- and polyfluoroalkyl substances (PFAS) in six human cell lines. Toxicology 40 35933025
2022 Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood. Environmental science & technology 39 35436088
2014 Tissue-specific and time-dependent regulation of the endothelin axis by the circadian clock protein Per1. Life sciences 39 24721511
2018 Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model. Systems biology in reproductive medicine 36 29911897
2022 Simulation modelling the structure related bioaccumulation and biomagnification of per- and polyfluoroalkyl substances in aquatic food web. The Science of the total environment 35 35660442
2021 Per- and polyfluoroalkyl substances (PFAS) augment adipogenesis and shift the proteome in murine 3T3-L1 adipocytes. Toxicology 35 34800597
2015 EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription. Scientific reports 35 26471974
2010 Electrophysiological effects of melatonin on mouse Per1 and non-Per1 suprachiasmatic nuclei neurones in vitro. Journal of neuroendocrinology 34 20819119
2020 Binding of Per- and Polyfluoroalkyl Substances to the Human Pregnane X Receptor. Environmental science & technology 33 33228354
2013 Fictibacillus phosphorivorans gen. nov., sp. nov. and proposal to reclassify Bacillus arsenicus, Bacillus barbaricus, Bacillus macauensis, Bacillus nanhaiensis, Bacillus rigui, Bacillus solisalsi and Bacillus gelatini in the genus Fictibacillus. International journal of systematic and evolutionary microbiology 33 23355698
2023 Neurodegeneration cell per cell. Neuron 32 36787752
2023 Degradation and Defluorination of Per- and Polyfluoroalkyl Substances by Direct Photolysis at 222 nm. ACS ES&T water 32 37588805
2022 Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2). Toxicology 32 36341878
2023 Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst. Journal of immunotoxicology 30 36788734
2021 Combined effects of mixed per- and polyfluoroalkyl substances on the Nrf2-ARE pathway in ARE reporter-HepG2 cells. Journal of hazardous materials 30 34388917
2013 Role of Per1 and the mineralocorticoid receptor in the coordinate regulation of αENaC in renal cortical collecting duct cells. Frontiers in physiology 30 24062694
2025 Decoding per- and polyfluoroalkyl substances (PFAS) in hepatocellular carcinoma: a multi-omics and computational toxicology approach. Journal of translational medicine 29 40317014
2024 Adverse outcome pathway for the neurotoxicity of Per- and polyfluoroalkyl substances: A systematic review. Eco-Environment & Health 27 39605965
2022 Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines. International journal of molecular sciences 27 35563566
2021 Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats. Environmental science and pollution research international 27 33745045
2004 Regulation of photoreceptor Per1 and Per2 by light, dopamine and a circadian clock. The European journal of neuroscience 27 15245489
2023 Dietary exposure to per- and polyfluoroalkyl substances: Potential health impacts on human liver. The Science of the total environment 26 37871818
2012 Sphingopyxis rigui sp. nov. and Sphingopyxis wooponensis sp. nov., isolated from wetland freshwater, and emended description of the genus Sphingopyxis. International journal of systematic and evolutionary microbiology 25 22798653
2024 Suspect, Nontarget Screening, and Toxicity Prediction of Per- and Polyfluoroalkyl Substances in the Landfill Leachate. Environmental science & technology 24 38408453
2022 Uptake, distribution, and depuration of emerging per- and polyfluoroalkyl substances in mice: Role of gut microbiota. The Science of the total environment 24 36041619
2021 The Circadian Protein PER1 Modulates the Cellular Response to Anticancer Treatments. International journal of molecular sciences 24 33804124
2021 PER2 mediates CREB-dependent light induction of the clock gene Per1. Scientific reports 24 34741086
2019 Circadian gene PER1 senses progesterone signal during human endometrial decidualization. The Journal of endocrinology 24 31518992
2023 The clock gene Per1 may exert diurnal control over hippocampal memory consolidation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 37264172
2024 Involvement of per- and polyfluoroalkyl compounds in tumor development. Archives of toxicology 22 38478087
2020 Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort. The Journal of clinical endocrinology and metabolism 22 32620010
2024 Removal of per- and polyfluoroalkyl substances from water by plasma treatment: Insights into structural effects and underlying mechanisms. Water research 21 38377926
2023 Per- and polyfluoroalkyl substances and cardiometabolic diseases: A review. Basic & clinical pharmacology & toxicology 21 37817473
2021 Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells. Biochemical pharmacology 21 34968493
2020 Exposure to per- and polyfluoroalkyl substances and premature skin aging. Journal of hazardous materials 21 33129602
2022 Glioma is associated with exposure to legacy and alternative per- and polyfluoroalkyl substances. Journal of hazardous materials 20 36084455
2008 PERspective on PER phosphorylation. Genes & development 20 18593875
2024 Immunotoxicity of legacy and alternative per- and polyfluoroalkyl substances on zebrafish larvae. Environmental pollution (Barking, Essex : 1987) 19 38977121
2023 Dietary per- and polyfluoroalkyl substance (PFAS) exposure in adolescents: The HOME study. Environmental research 19 37142081
2023 Comparative developmental toxicities of zebrafish towards structurally diverse per- and polyfluoroalkyl substances. The Science of the total environment 19 37633367
2023 Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater. Environmental science & technology 19 37648245
2015 Real-Time Recording of Circadian Per1 and Per2 Expression in the Suprachiasmatic Nucleus of Freely Moving Rats. Journal of biological rhythms 18 26656624
2022 Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice. International journal of molecular sciences 17 35806403
2022 Toxicokinetic Modeling of Per- and Polyfluoroalkyl Substance Concentrations within Developing Zebrafish (Danio rerio) Populations. Environmental science & technology 17 36055240
2022 Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition. Environmental epidemiology (Philadelphia, Pa.) 16 36777525
2016 Differential localization of PER1 and PER2 in the brain master circadian clock. The European journal of neuroscience 16 27740710
2024 Identifying novel mechanisms of per- and polyfluoroalkyl substance-induced hepatotoxicity using FRG humanized mice. Archives of toxicology 15 38782768
2024 Aerobic or anaerobic? Microbial degradation of per- and polyfluoroalkyl substances: A review. Journal of hazardous materials 15 39467433
2023 Per- and polyfluoroalkyl substances (PFAS) inhibit cytochrome P450 CYP3A7 through direct coordination to the heme iron and water displacement. Journal of inorganic biochemistry 15 36638633
2022 LncRNA TPTEP1 inhibits the migration and invasion of gastric cancer cells through miR-548d-3p/KLF9/PER1 axis. Pathology, research and practice 15 35985238
2010 Cell biology through proteomics--ad astra per alia porci. Trends in cell biology 15 20227883