Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 28 for “"PER2"”.
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The Translationally Controlled Tumor Protein (TCTP) associates to and destabilizes the Circadian Factor Period 2 (Per2)
Period 2 (Per2) is a core circadian factor responsible for its own negative regulation. It operates in the circadian clock, which affects multiple biological functions such as metabolic rate, hormone release, and core body temperature. The Per2 protein functions directly with factors in other …
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Insights on the Regulation of the PERIOD 2 Gene in the Cellular Response to DNA Damage
… synchrony with environmental changes. PERIOD2 (PER2) is a core component of the circadian clock and a candidate tumor suppressor as its knockout expression results in a cancer-prone animal. p53 is an effector in the DNA damage response and regulates downstream effectors by trans-activation. …
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Identification and Regulatory Role of E3 Ligases in the Time-Dependent Degradation of the Circadian Factor Period 2
… 2-3) focuses on the function of Period 2 (Per2), a key regulatory component of the negative feedback arm of the clock and tumor suppressor protein, as a modulator of cell cycle response. We found that Per2 binds the C-terminus end of the tumor suppressor p53 thus forming a trimeric complex …
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Circadian Control of Cell Cycle Progression
… of cell cycle checkpoints 1. Period 2 (Per2) is a tumor suppressor that oscillate in expression in a 24-hour cycle 2, 3. Here, we show that Per2 interacts with the tumor suppressor protein p53. Both G1 and G2 checkpoint pathways involve a p53 dependent pathway which can trigger the cell …
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Circadian modulation of the estrogen receptor alpha transcription
… (e.g. jet lag, insomnia, and cancer). Period 2 (Per2), a circadian protein, is at the center of the clock's function. The loss or deregulation of per2 has been shown to be common in several types of cancer including breast and ovarian [1, 2]. Epidemiological studies established a correlation …
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Investigation into the molecular mechanisms underlying circadian rhythm disruption and human cancer
Human Period2 (PER2) is one of the core mammalian clock factors known to be rhythmically expressed throughout the body and directly binds to the tumor suppressor p53 and its negative regulator, the oncogenic mouse double minute-2 (MDM2) protein. PER2 modulates p53 transcriptional activity by …
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Interlocking mechanisms regulating the circadian clock response to DNA damage
… that the core clock component PERIOD2 (PER2) binds to the tumor suppressor protein p53, a key regulatory checkpoint component that modulates cell cycle progression and the cellular response to genotoxic stress. PER2 binding to p53 modulates p53's stability, cellular localization, and …
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Biological Clocks, Inflammation, and Multiorgan Damage In Sickle Cell Disease
… genes in SCD lung. <em>Period 2</em> <em>(Per2)</em>, a circadian gene, was increased in SCD. To test whether<em> Per2</em> mRNA and PER2 protein levels were further induced in sickle lung, I utilized a genetic tool<em>, Per2 <sup>Luciferase</sup></em> (<em>Per2<sup>Luc</sup></em>) mice, a …
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Functional investigation of PERIOD in the mammalian circadian clock
… understanding for the rhythmic functions of PER2 in human cells, by first assessing the roles of rhythmic Per transcription and rhythmic PER protein abundance in driving circadian rhythmicity. Finally, I aimed to explore how the rhythmic activity of PER helps drives circadian rhythmicity. The …
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Molecular Mechanisms of Melatonin Action on the Rat Suprachiasmatic Nucleus: An in Vitro Analysis
… that the induction of the dock genes Per1 and Per2 is necessary for melatonin to elicit a phase advance in neural activity, an effect that is abolished by inhibiting PKC. Furthermore, the effects of melatonin on Per1 and Per2 are mediated by cis-acting regulatory enhancer sequences termed …
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Signal Transduction Mechanisms Of Pas And Hamp Domains
… is the identification of two core clock genes, PER2 and nPAS2, as heme-binding PAS proteins. A complicated feedback mechanism has been suggested where cycles in heme availability feedback to regulate the activity of PER2 and nPAS2. In chapter 2, I present data that PER2-heme interactions are …
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The roles of vasoactive intestinal polypeptide in circadian entrainment of suprachiasmatic nucleus
… extensively. We recorded PERIOD::LUCIFERASE: PER2::LUC) expression from SCN explant cultures over multiple days following VIP application at different circadian time points to generate a phase response curve which reliably predicted the phase relationship between the SCN and daily increases in …
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Chronotype in the South African population: the influence of longitudinal location
… and allelic frequency distributions of the PER2 single nucleotide polymorphism (SNP) G3853A (rs934945) in the Eastern (n= 184) and Western (n=186) populations, and the PER3 variable number tandem repeat (VNTR) polymorphism in the Eastern (n=143) and Western (n=176) populations from buccal …
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Circadian Orchestration of the Cellular Proteome
… the circadian regulation of the PERIOD 2 (PER2) protein in CRY-deficient cells, suggesting that a key determinant of PER2 behaviour in the absence of the TTFL may be cellular protein and ion concentrations. In the final chapter I investigated the functional consequences of CRY knock-out. I …
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Using Translational Switching to Investigate the SCN Clockwork
… switchable Bmal1 (tsBMAL1) and Period2 (tsPER2), as well as using a translationally switchable copy of CRY1 (tsCRY1) developed previously in the lab, to investigate the SCN clockwork. First, I show how generation of tsBMAL1 provided conditional and reversible control of transgenic …
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Architecture of the Mammalian Circadian Repressive Complex
… with CRY2 is strengthened by co-expression of PER2, suggesting that PER expression limits the length of the repressive phase in CRY2-driven rhythms. In order to better understand PER's role, we collaborated with another lab to solve and validate a structure of CRY2 bound to a fragment of PER. …
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Circadian desynchrony in the mouse: how does chronic exposure to rotating shift work-like patterns of light/dark affect circadian rhythms and neurobehavioural outcomes
… of core molecular clock proteins PER1 and PER2. Together these observations suggest that major alterations in circadian rhythm components are induced by light/dark cycles which resemble shift work and are predictive of long term changes in behaviour and learning which persist after …
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Metabolic Regulation of Circadian Timekeeping
… and elicits induction of clock protein PER2. Strikingly, manipulation of insulin signalling is sufficient to determine all the essential parameters of the cellular clock (phase, period and amplitude) in a dose-dependent but glucose independent fashion. Using pharmacological and genetic …
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Time of Day Influences on Gonadotropin Releasing Hormone Neurons
… found that mouse GnRH neurons express period 2 (Per2) and brain muscle ARNT like protein (Bmal) with a circadian period, and thus likely run a functional molecular clock. Further, vasoactive intestinal peptide (VIP), but not arginine vasopressin (AVP), was capable of synchronizing clock gene …
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Investigation of the Signaling Mechanisms of the Pineal Hormone Melatonin in the in Vitro Rat Suprachiasmatic Nucleus
… on each of three clock gene rnRNAs---Per1, Per2, and Tim. Overall, melatonin was shown to modulate the SCN clock during two windows of sensitivity, by inducing a complex signal cascade involving specific receptors, second messengers, protein kinases, and gene transcription.
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