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Showing PER1 — PER is a alias.

PER1

Period circadian protein homolog 1 · UniProt O15534

Audit flag: ungrounded claim
Length
1290 aa
Mass
136.2 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PER1 is a bHLH/PAS domain protein that constitutes a core component of the mammalian circadian negative feedback loop, expressed rhythmically in the suprachiasmatic nucleus where its oscillation persists in constant darkness and entrains to light/dark cycles (PMID:9323128). Its transcription is gated by chromatin dynamics and light-responsive promoter elements: CRY1 represses Per1 by recruiting HDACs and mSin3B, while light pulses drive rapid histone H3/H4 acetylation and phospho-CREB binding at the Per1 promoter (PMID:15226430), and a CRE element is required in vivo for light-induced Per1 expression in the SCN (PMID:32807491), with PER2 acting as a CREB co-factor that stabilizes the CREB-CRTC1-CBP complex to enable stimulus-dependent Per1 induction (PMID:34741086). At the protein level PER1 serves as a scaffold for casein kinase 1, and disrupting the PER-CK1 interaction abolishes PER phosphorylation and CLOCK hyperphosphorylation and stabilizes PER, though core rhythmicity can persist via PER-CRY-dependent feedback independent of PER abundance rhythms (PMID:35810166). Beyond the central clock, PER1 functions as a tissue-level regulator of proliferation and metabolism in cancer, suppressing tumor growth by forming a PER1/RACK1/PI3K complex that accelerates PI3K degradation and inhibits PI3K/AKT-driven glycolysis (PMID:23723221), by physically engaging p53 in mutual negative cross-regulation that modulates apoptosis sensitivity (PMID:33804124), and by partnering with PPARγ to drive circadian HK2-dependent glycolysis (PMID:35255118). PER1 additionally controls developmental and physiological programs through chromatin-based transcriptional activation, promoting myoblast differentiation and muscle regeneration via Pol II recruitment and histone remodeling at the Igf2 locus (PMID:34009269), supporting human endometrial decidualization downstream of progesterone receptor (PMID:31518992), and regulating hippocampal spatial memory consolidation locally and independently of its circadian role (PMID:37264172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Established that a mammalian period ortholog exists and operates as a circadian-regulated gene, defining the molecular entry point for the mammalian clock.

    Evidence cDNA cloning, sequence homology to Drosophila PERIOD, and in situ hybridization in SCN under constant darkness and shifted light/dark cycles

    PMID:9323128

    Open questions at the time
    • Protein-level partners and repressor mechanism not yet defined
    • Does not address how light entrains Per1 transcription
  2. 1999 Medium

    Showed that Per1 in the pars tuberalis encodes photoperiodic information through amplitude rather than phase, extending its role to seasonal timing.

    Evidence In situ hybridization of Per1 mRNA in pars tuberalis under long/short photoperiods in Syrian hamsters

    PMID:10449798

    Open questions at the time
    • Single method (in situ hybridization)
    • Molecular link from melatonin signaling to Per1 amplitude not resolved
  3. 2001 Medium

    First linked PER1 to hypoxia signaling by demonstrating a physical interaction with HIF-1α and tissue-specific PER1 isoforms.

    Evidence Co-immunoprecipitation of PER1 and HIF-1α, subcellular fractionation, and temporal/tissue Western blots in mouse brain and kidney

    PMID:11726537

    Open questions at the time
    • Single co-IP without reciprocal validation
    • Functional consequence of PER1-HIF-1α interaction not established
  4. 2004 High

    Defined the chromatin basis of Per1 regulation, showing repression via CRY1-recruited HDAC/mSin3B and light-induced activation through histone acetylation and CREB binding.

    Evidence ChIP for histone acetylation at Per1 promoter, TSA treatment in vivo and in vitro, luciferase reporters, and co-IP of CRY1 with HDACs/mSin3B

    PMID:15226430

    Open questions at the time
    • Promoter element mediating CREB-dependent induction not yet genetically defined
    • Co-factors of CREB at the locus not identified
  5. 2007 Medium

    Demonstrated steroid hormone control of Per1, showing estradiol and progesterone induce Per1 in distinct uterine compartments via their receptors.

    Evidence Ovariectomized rat model with hormone administration, in situ hybridization, and receptor antagonist (ICI182780, RU486) experiments

    PMID:17761890

    Open questions at the time
    • Direct receptor binding to the Per1 promoter not shown
    • Physiological consequence in the uterus not defined
  6. 2016 Medium

    Identified a tumor-suppressive role for Per1 in cholangiocarcinoma and placed it under miR-34a control, expanding its function to cell-cycle and apoptosis regulation.

    Evidence Per1 overexpression constructs, in vitro proliferation/apoptosis/cell-cycle assays, xenograft tumor growth, miRNA target validation, and mRNA profiling

    PMID:26923637

    Open questions at the time
    • Direct molecular effectors downstream of Per1 not defined
    • Single tumor type and lab
  7. 2019 High

    Showed PER1 senses progesterone during decidualization, with PR directly activating PER1, which in turn stabilizes FOXO1 to support decidual transformation.

    Evidence ChIP of PR at PER1 promoter, PER1 knockout in human endometrial stromal cells, decidualization and FOXO1 stability assays

    PMID:31518992

    Open questions at the time
    • Mechanism by which PER1 stabilizes FOXO1 not defined
    • Not connected to circadian oscillation of PER1 in this tissue
  8. 2021 High

    Resolved how Per1/Per2 drive myoblast differentiation by activating Igf2 transcription through Pol II recruitment, histone remodeling, and promoter-enhancer looping.

    Evidence siRNA depletion in vitro, in vivo muscle regeneration, ChIP (H3K4me3, H3K27ac, Pol II at Igf2), and chromosome conformation capture

    PMID:34009269

    Open questions at the time
    • Per1-specific versus Per2-specific contributions only partly separated
    • How Per1 is recruited to the Igf2 locus not defined
  9. 2021 High

    Identified the PER1/RACK1/PI3K complex as the mechanism by which PER1 suppresses glycolysis and proliferation, accelerating PI3K degradation to dampen PI3K/AKT signaling.

    Evidence Co-IP, cycloheximide chase, stable OE/KD/mutant lines, AKT and glycolysis pharmacological rescue, and xenograft assay in OSCC

    PMID:23723221

    Open questions at the time
    • Whether complex formation is circadian-gated not addressed
    • Structural basis of PER1-RACK1-PI3K assembly unknown
  10. 2021 Medium

    Established mutual negative cross-regulation between PER1 and p53, linking the clock protein to apoptosis sensitivity in cancer.

    Evidence Co-IP of PER1-p53, p53 stability and transcription assays, in vitro apoptosis assays, and NSG xenograft model

    PMID:33804124

    Open questions at the time
    • Domain mediating PER1-p53 interaction not mapped
    • Mechanism of reciprocal p53 repression of PER1 not defined
  11. 2021 Medium

    Clarified how Per1 light induction is achieved, showing PER2 acts as a CREB co-factor that stabilizes CREB-CRTC1-CBP complex formation and enables Pol II recruitment at Per1.

    Evidence Co-IP of CREB-CRTC1-CBP, ChIP (H3K9ac, Pol II) at Per1, Per2 KO mice, and light/forskolin stimulation

    PMID:34741086

    Open questions at the time
    • Direct PER2-CREB contact versus indirect bridging not distinguished
    • Generalizability beyond SCN/light induction not tested
  12. 2020 High

    Genetically defined the CRE element in the Per1 promoter as necessary for light-induced Per1 expression in the SCN, validating the CREB-dependent photic input pathway in vivo.

    Evidence CRISPR knock-in CRE-deleted mice, in situ hybridization of Per1/Per2 after light pulse, and behavioral rhythm analysis

    PMID:32807491

    Open questions at the time
    • Other promoter elements contributing to residual induction not characterized
    • Behavioral phenotype of CRE deletion only partly resolved
  13. 2022 High

    Resolved PER1's role at the protein level as a CK1 scaffold and uncoupled period length from PER phosphorylation and abundance rhythms via a PER-CRY-dependent feedback mechanism.

    Evidence Mutagenesis of PER-CK1 interaction residues, cellular phosphorylation assays, and mutant mice with locomotor and molecular rhythm analysis

    PMID:35810166

    Open questions at the time
    • Molecular basis of the phosphorylation-independent PER-CRY feedback not defined
    • How residual rhythmicity is generated without PER abundance oscillation unclear
  14. 2022 Medium

    Connected PER1 to chemoresistance by showing a PER1/PPARγ complex drives circadian HK2-dependent glycolysis, and that silencing PER1 reverses trastuzumab resistance.

    Evidence PER1 silencing in vitro and in vivo, circadian glycolysis measurements, PPARγ-PER1 complex assay, and metformin/trastuzumab combination timing

    PMID:35255118

    Open questions at the time
    • Apparent pro-glycolytic role contrasts with glycolysis suppression in other tumors; context-dependence not reconciled
    • Direct PER1-PPARγ binding interface not mapped
  15. 2022 Medium

    Linked clock function to steroidogenesis, showing Per1/Per2 loss reduces testosterone synthesis through the PKA-StAR pathway in aging male mice.

    Evidence Per1/Per2 DKO mouse model, plasma testosterone metabolomics, testis transcriptomics, Western blot (StAR, p-CREB, PKA, AC1), and sperm motility

    PMID:35806403

    Open questions at the time
    • Per1-specific contribution not isolated from Per2 in this DKO
    • Direct molecular target of PER1 in the PKA-StAR pathway not identified
  16. 2023 Medium

    Demonstrated a clock-independent role for Per1 in the hippocampus, where local knockdown impairs spatial memory consolidation without affecting circadian or sleep behavior.

    Evidence Hippocampus-specific Per1 knockdown, Object Location Memory across day/night, RNA-seq, and analysis of diurnal Per1 oscillation

    PMID:37264172

    Open questions at the time
    • Downstream transcriptional targets mediating consolidation not defined
    • Molecular partners of PER1 in hippocampal neurons unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PER1's many context-specific protein complexes (CK1, RACK1/PI3K, p53, PPARγ) are coordinated with its circadian oscillation and whether they share a common structural mode of engagement.
  • No structural model of PER1 complex assembly across contexts
  • Reconciliation of opposing pro- and anti-glycolytic roles across tumor types absent
  • Whether non-circadian functions depend on the core clock machinery undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9909396 Circadian clock 4
Partners
CSNK1HIF1APER2PIK3PPARGRACK1TP53
Complex memberships
PER1/PPARγ transcriptional complexPER1/RACK1/PI3K complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 RIGUI/PER1 encodes a bHLH/PAS domain protein 44% homologous to Drosophila PERIOD and is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN); circadian expression persists in constant darkness and shifts proportionally with light/dark cycle changes, establishing it as a mammalian ortholog of the Drosophila period gene involved in circadian clock regulation. cDNA cloning, sequence homology analysis, in situ hybridization in SCN under constant darkness and shifted light/dark cycles Cell High 9323128
2004 Circadian and light-induced transcription of Per1 depends on histone acetylation/deacetylation: CRY1 represses Per1 transcription by recruiting HDACs and mSin3B; light pulses induce rapid histone H3/H4 acetylation at the Per1 promoter in the SCN; HDAC inhibitor TSA induces endogenous Per1 expression and histone acetylation; phospho-CREB binds the CRE element of Per1 after light exposure. ChIP assay (histone acetylation at Per1 promoter), HDAC inhibitor (TSA) treatment, luciferase reporter assays, lateral ventricle TSA administration in vivo, co-immunoprecipitation of CRY1 with HDACs/mSin3B Molecular and cellular biology High 15226430
1999 Per1 expression in the pars tuberalis (PT) encodes photoperiodic time via melatonin-regulated amplitude: both long and short photoperiods produce a transient Per1 peak at ZT3 in the PT, but the amplitude is greatly attenuated under short photoperiod, demonstrating that melatonin signal duration controls Per1 amplitude rather than phase in this tissue. In situ hybridization of Per1 mRNA in PT under long/short photoperiods in Syrian hamsters; comparison of peak timing and amplitude Proceedings of the National Academy of Sciences of the United States of America Medium 10449798
2001 PER1 protein physically interacts with HIF-1α (the alpha subunit of hypoxia-inducible factor 1) as shown by co-immunoprecipitation; hypoxia increases PER1 and CLOCK protein levels in mouse brain; a predominantly nuclear 48 kDa PER1 isoform follows a daily rhythm in mouse brain, while a 55 kDa form is found in kidney. Co-immunoprecipitation of PER1 and HIF-1α, subcellular fractionation, Western blot with tissue-specific and temporal analysis FASEB journal Medium 11726537
2022 PER1 acts as a scaffold for CK1 in the circadian feedback mechanism: residues essential for PER-CK1 interaction were identified; their mutation abolishes PER phosphorylation and CLOCK hyperphosphorylation, resulting in PER stabilization and arrhythmic PER abundance, impairing negative feedback. Paradoxically, mutant mice show robust short-period locomotor rhythms, indicating the clock can function independently of PER phosphorylation and abundance rhythms via a PER-CRY-dependent feedback mechanism; period length is uncoupled from PER stability. Mutagenesis of PER-CK1 interaction residues, cellular assays, generation and analysis of mutant mice (locomotor activity, molecular rhythms), phosphorylation assays Nature communications High 35810166
2016 Per1 overexpression in cholangiocarcinoma cells decreases cell proliferation, induces apoptosis, lowers G2/M arrest, and reduces tumor growth in vivo; Per1 is a direct target of miR-34a, which rhythmically oscillates in cholangiocarcinoma cells; inhibition of miR-34a also decreases proliferation and invasion; mRNA profiling shows Per1 overexpression regulates cell cycle, growth, and apoptosis pathways. Per1 overexpression constructs, in vitro proliferation/apoptosis/cell cycle assays, in vivo xenograft tumor growth, miRNA target validation, mRNA profiling Journal of hepatology Medium 26923637
2021 PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma (OSCC) by forming a PER1/RACK1/PI3K protein complex: co-immunoprecipitation showed PER1 binds RACK1 and PI3K; PER1 overexpression increased complex abundance and decreased PI3K half-life (accelerating PI3K degradation), inhibiting PI3K/AKT signaling and glycolysis; these effects were reversed by PER1 mutation. In vivo tumorigenicity assays confirmed that PER1 overexpression suppresses tumor growth. Co-immunoprecipitation, cycloheximide chase (protein stability), stable OE/KD/mutation cell lines, AKT activator/inhibitor rescue experiments, glycolysis inhibitor experiments, in vivo xenograft assay Cell death & disease High 23723221
2021 Per1 and Per2 are required for proper myoblast differentiation and muscle regeneration: depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo (nonredundant functions). Both Per1 and Per2 activate Igf2 transcription (an autocrine promoter of myoblast differentiation) via Per-dependent RNA polymerase II recruitment, dynamic histone modifications at the Igf2 promoter and enhancer, and promoter-enhancer interaction. Muscle regeneration is faster when initiated at night when Per1, Per2, and Igf2 are highly expressed. siRNA depletion in vitro, in vivo muscle regeneration assay, ChIP (H3K4me3, H3K27ac, RNA Pol II at Igf2 locus), chromosome conformation capture (promoter-enhancer interaction), diurnal timing experiments The Journal of cell biology High 34009269
2019 The circadian gene PER1 senses progesterone signaling during human endometrial decidualization: the progesterone receptor (PR) directly binds the PER1 promoter to activate its transcription at the onset of stromal proliferation-differentiation transition; PER1 knockout significantly attenuated decidual transformation by expediting FOXO1 protein degradation and downregulating PR target genes. ChIP (PR binding to PER1 promoter), PER1 knockout in human endometrial stromal cells, decidualization assays, FOXO1 protein stability analysis, RT-PCR The Journal of endocrinology High 31518992
2022 In trastuzumab-resistant HER2-positive gastric cancer, PER1 forms a transcriptional complex with PPARγ that drives circadian oscillation of HK2 (hexokinase 2)-dependent glycolysis; silencing PER1 disrupts PER1-HK2 circadian rhythm and reverses trastuzumab resistance; metformin, which inhibits glycolysis and PER1, combined with trastuzumab at ZT6, improved trastuzumab efficacy. PER1 silencing in vitro and in vivo, circadian glycolysis measurements (ZT6 vs ZT18), co-immunoprecipitation/transcriptional complex assay (PPARγ-PER1), combinatorial drug treatment with metformin Cancer research Medium 35255118
2021 PER1 physically interacts with p53 to reduce p53 stability and impair its transcriptional activity; conversely, p53 represses PER1 transcription (mutual negative cross-regulation); PER1 reduced sensitivity of cancer cells to drug-induced apoptosis both in vitro and in vivo in xenograft mouse models. Co-immunoprecipitation (PER1-p53 physical interaction), p53 stability and transcription assays, in vitro apoptosis assays with anticancer drugs, in vivo NSG mouse xenograft model International journal of molecular sciences Medium 33804124
2021 PER2 acts as a co-factor of CREB to facilitate light/forskolin-induced transcription of Per1: PER2 modulates the interaction between CREB and its co-regulator CRTC1, supporting complex formation only after stimulus; absence of PER2 abolished CBP-CREB interaction, reduced histone H3 acetylation, and decreased RNA Pol II recruitment to the Per1 gene. In vitro and in vivo (mouse) approaches; co-immunoprecipitation (CREB-CRTC1-CBP complex), ChIP (H3K9ac, RNA Pol II at Per1), Per2 knockout mice, light/forskolin stimulation Scientific reports Medium 34741086
2020 A cAMP response element (CRE) in the Per1 promoter is necessary for light-induced Per1 expression in the SCN at night: CRE-deleted mice showed blunted light-induced Per1 mRNA expression in the SCN, establishing the CRE as the functional element mediating CREB-dependent Per1 induction by light. CRISPR/knock-in generation of CRE-deleted mice in Per1 and Per2 promoters, in situ hybridization of Per1/Per2 mRNA after light pulse, behavioral rhythm analysis Biochemical and biophysical research communications High 32807491
2007 Estradiol (E2) and progesterone (P4) upregulate Per1 expression in rat uterus in a compartment-specific manner: E2 induces Per1 in luminal epithelium, glandular epithelium, and myometrium; P4 induces Per1 in luminal epithelium, glandular epithelium, and stroma; these effects are blocked by antagonists ICI182780 (anti-estrogen) and RU486 (anti-progestin), establishing steroid hormone-receptor-dependent regulation of Per1. Ovariectomized rat model, steroid hormone administration, in situ hybridization and immunofluorescence, receptor antagonist experiments, RT-PCR in cultured uterine stromal cells The Journal of endocrinology Medium 17761890
2023 Local knockdown of Per1 within the dorsal hippocampus (DH) impairs spatial memory consolidation without affecting circadian rhythm or sleep behavior, demonstrating that Per1 functions independently within the DH to regulate memory consolidation in a diurnal manner; learning-induced Per1 oscillates in tandem with memory performance in the hippocampus. Hippocampus-specific Per1 knockdown (local injection), Object Location Memory task at multiple time points across day/night cycle, RNA-sequencing, analysis of diurnal Per1 oscillation in DH Neuropsychopharmacology Medium 37264172
2022 Per1/Per2 double knockout (DKO) reduces testosterone synthesis and impairs fertility in elderly male mice by downregulating steroid hormone synthesis enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, StAR) in the PKA-StAR pathway; Western blot showed reduced StAR, p-CREB, PKA, and AC1 in testicular tissue of DKO mice, linking circadian clock disruption to impaired steroidogenesis. Per1/Per2 DKO mouse model, hormone-targeted metabolomics (plasma testosterone), transcriptomic analysis of testis, Western blot (StAR, p-CREB, PKA, AC1), sperm motility assay International journal of molecular sciences Medium 35806403
2014 In Drosophila, PDF neuropeptide increases cAMP and PKA activity to stabilize PER protein: increasing cAMP/PKA stabilizes PER in S2 cells and in fly circadian neurons; PDF applied to fly brains in vitro similarly stabilizes PER; the per(S) mutant (short half-life PER) ameliorates pdf-null phenotypes, placing PDF-cAMP-PKA upstream of PER stability in setting circadian period. Genetic epistasis (per(S) suppressor of pdf-null), cell-based PER stability assays in S2 cells with PKA manipulation, ex vivo brain PDF application, immunostaining of PER in circadian neurons Proceedings of the National Academy of Sciences of the United States of America Medium 24707054

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 559 9323128
2005 Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis 313 15790588
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 198 36814257
2004 Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Molecular and cellular biology 163 15226430
2021 Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma. Journal of the National Cancer Institute 160 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 148 37126916
2020 Uptake and accumulation of per- and polyfluoroalkyl substances in plants. Chemosphere 125 32717507
2021 Exposure routes, bioaccumulation and toxic effects of per- and polyfluoroalkyl substances (PFASs) on plants: A critical review. Environment international 107 34592655
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 104 35921496
2021 Epigenetic changes by per- and polyfluoroalkyl substances (PFAS). Environmental pollution (Barking, Essex : 1987) 103 33751946
2022 Per- and Polyfluoroalkyl Substances (PFASs) Impair Lipid Metabolism in Rana nigromaculata: A Field Investigation and Laboratory Study. Environmental science & technology 102 36044002
2021 A Review of Per- and Polyfluorinated Alkyl Substance Impairment of Reproduction. Frontiers in toxicology 92 35295153
2023 Occurrence and Bioaccumulation Patterns of Per- and Polyfluoroalkyl Substances (PFAS) in the Marine Environment. ACS ES&T water 91 37261084
2022 Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer. Cancer research 83 35255118
2016 miR-34a-dependent overexpression of Per1 decreases cholangiocarcinoma growth. Journal of hepatology 81 26923637
2022 Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with oxidative stress biomarkers during pregnancy. Environment international 80 36191484
2020 Per- and Polyfluoroalkyl-Contaminated Freshwater Impacts Adjacent Riparian Food Webs. Environmental science & technology 77 32870664
2016 The Evolution of Per-cell Organelle Number. Frontiers in cell and developmental biology 75 27588285
2019 Per-Nucleus Crossover Covariation and Implications for Evolution. Cell 67 30879787
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
2001 Expression of the Per1 gene in the hamster: brain atlas and circadian characteristics in the suprachiasmatic nucleus. The Journal of comparative neurology 67 11169484
2020 Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion In Vitro. Toxicological sciences : an official journal of the Society of Toxicology 64 32219433
2021 PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex. Cell death & disease 56 33723221
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
2023 Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae. Environment international 55 37244004
2007 Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus. The Journal of endocrinology 54 17761890
2022 Per- and polyfluoroalkyl substances activate UPR pathway, induce steatosis and fibrosis in liver cells. Environmental toxicology 53 36251517
2023 Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment. Chemical research in toxicology 49 37184865
2022 Distribution of per- and poly-fluoroalkyl substances and their precursors in human blood. Journal of hazardous materials 49 36115093
2021 Tumorigenic activity of alternative per- and polyfluoroalkyl substances (PFAS): Mechanistic in vitro studies. The Science of the total environment 48 34843762
2020 Challenges of aqueous per- and polyfluoroalkyl substances (PFASs) and their foreseeable removal strategies. Chemosphere 48 32120153
2007 Spirosoma rigui sp. nov., isolated from fresh water. International journal of systematic and evolutionary microbiology 44 18048741
2021 Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure. Toxics 43 34062743
2019 Cord blood Per- and polyfluoroalkyl substances, placental steroidogenic enzyme, and cord blood reproductive hormone. Environment international 43 31174145
2022 Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood. Environmental science & technology 42 35436088
2022 Comparative cytotoxicity of seven per- and polyfluoroalkyl substances (PFAS) in six human cell lines. Toxicology 42 35933025
2021 Binding of Per- and Polyfluoro-alkyl Substances to Peroxisome Proliferator-Activated Receptor Gamma. ACS omega 41 34151090
2022 Decoupling PER phosphorylation, stability and rhythmic expression from circadian clock function by abolishing PER-CK1 interaction. Nature communications 37 35810166
2018 Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model. Systems biology in reproductive medicine 37 29911897
2010 Paenibacillus rigui sp. nov., isolated from a freshwater wetland. International journal of systematic and evolutionary microbiology 37 20382792
2021 Per- and polyfluoroalkyl substances (PFAS) augment adipogenesis and shift the proteome in murine 3T3-L1 adipocytes. Toxicology 36 34800597
2022 Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2). Toxicology 35 36341878
2021 Per1/Per2-Igf2 axis-mediated circadian regulation of myogenic differentiation. The Journal of cell biology 35 34009269
2012 Abnormal expression of PER1 circadian-clock gene in oral squamous cell carcinoma. OncoTargets and therapy 35 23226027
2023 Neurodegeneration cell per cell. Neuron 34 36787752
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
2025 Decoding per- and polyfluoroalkyl substances (PFAS) in hepatocellular carcinoma: a multi-omics and computational toxicology approach. Journal of translational medicine 32 40317014
2024 Adverse outcome pathway for the neurotoxicity of Per- and polyfluoroalkyl substances: A systematic review. Eco-Environment & Health 30 39605965
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
2023 Dietary exposure to per- and polyfluoroalkyl substances: Potential health impacts on human liver. The Science of the total environment 28 37871818
2021 Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats. Environmental science and pollution research international 28 33745045
2022 Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines. International journal of molecular sciences 27 35563566
2022 Uptake, distribution, and depuration of emerging per- and polyfluoroalkyl substances in mice: Role of gut microbiota. The Science of the total environment 26 36041619
2024 Suspect, Nontarget Screening, and Toxicity Prediction of Per- and Polyfluoroalkyl Substances in the Landfill Leachate. Environmental science & technology 25 38408453
2021 PER2 mediates CREB-dependent light induction of the clock gene Per1. Scientific reports 25 34741086
2019 Circadian gene PER1 senses progesterone signal during human endometrial decidualization. The Journal of endocrinology 25 31518992
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
2023 Dietary per- and polyfluoroalkyl substance (PFAS) exposure in adolescents: The HOME study. Environmental research 24 37142081
2023 The clock gene Per1 may exert diurnal control over hippocampal memory consolidation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 24 37264172
2021 The Circadian Protein PER1 Modulates the Cellular Response to Anticancer Treatments. International journal of molecular sciences 24 33804124
2021 Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells. Biochemical pharmacology 24 34968493
2022 Glioma is associated with exposure to legacy and alternative per- and polyfluoroalkyl substances. Journal of hazardous materials 23 36084455
2024 Removal of per- and polyfluoroalkyl substances from water by plasma treatment: Insights into structural effects and underlying mechanisms. Water research 22 38377926
2024 Involvement of per- and polyfluoroalkyl compounds in tumor development. Archives of toxicology 22 38478087
2023 Per- and polyfluoroalkyl substances and cardiometabolic diseases: A review. Basic & clinical pharmacology & toxicology 22 37817473
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
2020 Exposure to per- and polyfluoroalkyl substances and premature skin aging. Journal of hazardous materials 22 33129602
2008 PERspective on PER phosphorylation. Genes & development 22 18593875
2024 Immunotoxicity of legacy and alternative per- and polyfluoroalkyl substances on zebrafish larvae. Environmental pollution (Barking, Essex : 1987) 20 38977121
2023 Comparative developmental toxicities of zebrafish towards structurally diverse per- and polyfluoroalkyl substances. The Science of the total environment 20 37633367
2023 Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater. Environmental science & technology 20 37648245
2022 Exposure of Preconception Couples to Legacy and Emerging Per- and Polyfluoroalkyl Substances: Variations Within and Between Couples. Environmental science & technology 18 35016501
2022 Toxicokinetic Modeling of Per- and Polyfluoroalkyl Substance Concentrations within Developing Zebrafish (Danio rerio) Populations. Environmental science & technology 18 36055240
2024 Identifying novel mechanisms of per- and polyfluoroalkyl substance-induced hepatotoxicity using FRG humanized mice. Archives of toxicology 17 38782768
2024 Aerobic or anaerobic? Microbial degradation of per- and polyfluoroalkyl substances: A review. Journal of hazardous materials 17 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 17 36638633
2023 Binding of Per- and Polyfluoroalkyl Substances (PFAS) to the PPARγ/RXRα-DNA Complex. Journal of chemical information and modeling 17 37990410
2022 Per1/Per2 Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice. International journal of molecular sciences 17 35806403
2022 LncRNA TPTEP1 inhibits the migration and invasion of gastric cancer cells through miR-548d-3p/KLF9/PER1 axis. Pathology, research and practice 17 35985238
2009 Bacillus rigui sp. nov., isolated from wetland fresh water. International journal of systematic and evolutionary microbiology 17 19897614
2023 Mechanisms and Opportunities for Rational In Silico Design of Enzymes to Degrade Per- and Polyfluoroalkyl Substances (PFAS). Journal of chemical information and modeling 16 37981739
2024 Associations between per- and polyfluoroalkyl substances exposure and thyroid hormone levels in the elderly. The Science of the total environment 15 38340830
2024 Exposure to per- and polyfluoroalkyl substances and high-throughput proteomics in Hispanic youth. Environment international 15 38537583
2024 Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps. Journal of immunotoxicology 15 38712868
2023 Transplacental transport of per- and polyfluoroalkyl substances (PFAS): Mechanism exploration via BeWo cell monolayer model. Journal of hazardous materials 15 38278074
2022 Early-life exposure to per- and polyfluoroalkyl substances and infant gut microbial composition. Environmental epidemiology (Philadelphia, Pa.) 15 36777525
2024 Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway. Journal of ethnopharmacology 14 38513778
2024 Exploring Toxicity of Per- and Polyfluoroalkyl Substances (PFAS) Mixture Through ADMET and Toxicogenomic In Silico Analysis: Molecular Insights. International journal of molecular sciences 14 39596398
2022 Volatilization Potential of Per- and Poly-fluoroalkyl Substances from Airfield Pavements and during Recycling of Asphalt. Environmental toxicology and chemistry 14 35781701
2022 Photodynamic Priming Overcomes Per- and Polyfluoroalkyl Substance (PFAS)-Induced Platinum Resistance in Ovarian Cancer†. Photochemistry and photobiology 14 36148678
2022 Resistance to Cefiderocol Involved Expression of PER-1 β-Lactamase and Downregulation of Iron Transporter System in Carbapenem-Resistant Acinetobacter baumannii. Infection and drug resistance 14 36514799
2020 cAMP response element induces Per1 in vivo. Biochemical and biophysical research communications 14 32807491
2023 Detection of Per- and Polyfluoroalkyl Substances in High-Protein Food Products. Environmental toxicology and chemistry 13 37671839
2023 Per- and Poly-fluoroalkyl Substances and Bile Acid Profiles in Pregnant Women. Environmental science & technology 13 37821457

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