84-5156-21　BMAL1, phosphorylated (Ser42) 100ul　520612

特徴

• Transcriptional activator 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 approximately 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.
• ARNTL/BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway.
• Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM.
• Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR.
• Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms.
• Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth.
• Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit.
• Regulates the circadian expression of CIART and KLF11.
• The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism.
• Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors.
• The NPAS2-ARNTL/BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina.
• The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (PubMed:23229515).
• CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (PubMed:23229515).
• The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515).
• Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504).
• Applications:Suitable for use in Western Blot, Immunohistochemistry and ELISA.
• Other applications not tested.
• Recommended Dilution:Western Blot: 1:500-1:2000, incubate membrane with diluted antibody in TBS, 5% milk, 0.1% Tween20 at 4°C with gentle shaking, overnight
• Immunohistochemistry: 1:50-1:200ELISA (peptide): 1:20,000-1:40,000Optimal 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.