84-4048-80　Cryptochrome-2 (CRY2) 50ul　312120

特徴

• Transcriptional repressor which forms a core component of the circadian clock.
• The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of ~24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior.
• It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function.
• Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system.
• Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers').
• The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN.
• The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle.
• Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day.
• Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle).
• A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively.
• Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging.
• A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism.
• Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters.
• The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression.
• This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively.
• CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs.
• Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator.
• Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1.
• With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony.
• May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation.
• Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes.
• Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4.
• Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs).
• Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1.
• Represses the CLOCK-ARNTL/BMAL1 induced transcription of NAMPT.
• Applications:Suitable for use in ELISA, Western Blot and Immunohistochemistry.
• Other applications not tested.
• Recommended Dilution:Western Blot: 1:200-1000Immunohistochemistry: 1:20-1:200Optimal dilutions to be determined by the researcher.
• Storage and Stability:May be stored at 4°C for short-term only.
• Aliquot to avoid repeated freezing and thawing.
• Store at -20°C.
• Aliquots are stable for 12 months after receipt.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.