Disease relevance of PER2

• Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS) [1].
• We used immunohistochemical staining, methylation specific PCR and direct sequencing methods to analyze molecular changes in three most important genes, namely PER1, PER2 and PER3, in circadian rhythm in 55 cases of breast cancer of Taiwanese women [2].
• This is the first report of SHV-5 beta-lactamase in Salmonella spp. and also the first report of SHV-5 in India. The extended-spectrum beta-lactamases that have been reported in Salmonella spp. now include the Group 2 be enzymes SHV-2, SHV-5, TEM-3, TEM-25, TEM-27, CTX-M2, PER-1 and PER-2, and the Group 1 enzymes DHA-1 and CMY-2 [3].
• Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia [4].
• CTX-M-2 (or its variant) was detected in all Escherichia coli, Enterobacter aerogenes, Serratia marcescens, Proteus mirabilis, and Providencia stuartii strains, while PER-2 was detected in Enterobacter cloacae, E. aerogenes, and Klebsiella pneumoniae; SHV-related ESBL were found only in K. pneumoniae [5].

Psychiatry related information on PER2

• In humans, variations of the PER2 gene are associated with regulation of alcohol consumption [6].
• Case study: differences in human Per2 gene expression, body temperature, cortisol, and melatonin parameters in remission and hypersomnia in a patient with recurrent hypersomnia [7].

High impact information on PER2

• We show that phosphorylation at S662 leads to increased PER2 transcription and suggest that phosphorylation at another site leads to PER2 degradation [8].
• Altering CKIdelta dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate period through PER2 in vivo [8].
• A mutation in human Period 2 (hPER2), a gene crucial for resetting the central clock in response to light, is associated with familial advanced sleep phase syndrome (FASPS), an autosomal dominant condition with early morning awakening and early sleep times [8].
• Thus, a variant in human sleep behavior can be attributed to a missense mutation in a clock component, hPER2, which alters the circadian period [9].
• Both PER1 and PER2 proteins share several regions of homology with the Drosophila PER protein, including the protein dimerization PAS domain [10].

Chemical compound and disease context of PER2

• OBJECTIVE: To review the safety and efficacy of the very-low-dose combination of perindopril 2 mg and indapamide 0.625 mg (Per2/Ind0.625) in essential hypertension, in relation to blood pressure control and target-organ damage [11].

Biological context of PER2

• Mammalian PERIOD2 protein (PER2) is the product of a clock gene that controls circadian rhythms, because PER2-deficient mice have an arrhythmic phenotype [12].
• The PER gene deregulation is not caused by genetic mutations but most probably by methylation of the PER1 or PER2 promoter [2].
• We developed a non-invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion [13].
• A missense mutation in the human PER2 gene has previously been linked to advanced sleep phase syndrome (ASPS) [14].
• The E-box enhancer elements possible to regulate transcription of Per1 and Per2 genes were highly conserved in rats and mice [15].

Anatomical context of PER2

• Temporal and spatial distribution of immunoreactive PER1 and PER2 proteins in the suprachiasmatic nucleus and peri-suprachiasmatic region of the diurnal grass rat (Arvicanthis niloticus) [16].
• Pinealectomy does not affect diurnal PER2 expression in the rat limbic forebrain [17].
• Similar increases were seen in the mRNA levels for both per1 and per2 in prehypertrophic chondrocytes in metatarsal organotypic cultures within 2 h of exposure to PTH [18].
• In addition, RNAi-mediated Per2 knockdown caused a significant decrease of granzyme B and perforin levels in the rat derived NK cell line RNK16 [19].
• Expression profiles for Per2, Bmal1 and Cry1 were first determined in a synchronized equine cell line [20].

Associations of PER2 with chemical compounds

• Interestingly, despite normal melatonin and cortisol secretion patterns, two groups of subjects could be distinguished with significantly different mean PER2 and BMAL1 acrophases [21].
• We have investigated three other single-nucleotide polymorphisms in the hPER2 gene, one downstream of the transcription start site (C-1228T), one in exon 2 in the 5'-untranslated region (5'-UTR) (C111G), and one missense mutation (G3853A) causing a glycine to glutamine substitution in the predicted protein [14].
• The blunting of the PER2 rhythm at these phases of the cycle is abolished by ovariectomy and restored by phasic estrogen replacement suggesting that fluctuations in estrogen levels or their sequelae are necessary to produce these effects [22].
• Daily limited access to sucrose or saccharine in freely fed rats or scheduled access to saline in sodium-deprived rats had no effect on these PER2 rhythms [23].
• As with light, muscimol alters circadian phase, and daytime phase alterations induced by muscimol are associated with significant decreases in Per2 mRNA [24].

Regulatory relationships of PER2

• The NMDA receptor antagonist AP5 and the AMPA/kainate receptor antagonist DNQX inhibited the ability of light and NMDA to acutely increase Per2 mRNA levels in the SCN [25].
• Per2 has antisense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding RNAs with sense Alu elements, and Pol-III transcribed Alus [26].

Other interactions of PER2

• This article discusses approaches, limitations, and applicable protocols to study the regulation of cellular localization of mammalian clock proteins, with a particular focus on mammalian CRY1 and PER2 proteins [27].
• BMAL1 oscillated with approximately the same phase as PER2, instead of being anti-phasic as anticipated from data previously obtained in other peripheral tissues [21].
• CKIepsilon (casein kinase Iepsilon) has been postulated to prime PER2 for degradation [28].
• For instance, a point mutation in a human clock gene (Per2) was shown to produce the rare advanced sleep phase syndrome, whereas a functional polymorphism in Per3 is associated with the more frequent delayed sleep phase syndrome [29].
• These results suggest that the activation of NMDA receptor is a critical step for photic induction of Per1 and Per2 transcripts in the SCN, which are linked to a photic behavioral entrainment [30].

Analytical, diagnostic and therapeutic context of PER2

• The PER1 and PER2 daily profiles were measured in peripheral organs by Western blotting [31].
• Molecular oscillation of per1 and per2 genes in the rodent brain: an in situ hybridization and molecular biological study [15].
• Thyroidectomy alters the daily pattern of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats [32].
• Co-immunoprecipitation experiments showed that PER2 bound to PP1c in transfected HEK-293 cells [33].
• Addition of NPY to the brain slices in the subjective day resulted in reduction of Per1 and Per2 mRNA levels 0.5 and 2 h after treatment [34].

References