Cell Signaling Technology

Product Pathways - Chromatin Regulation / Epigenetics

CLOCK (D45B10) Rabbit mAb #5157

acetyltransferase   circadian rythm   HAT  

No. Size Price
5157S 100 µl ( 10 western blots ) ¥3,100.00 现货查询 购买询价
5157 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Mouse,Monkey, Endogenous 100 Rabbit IgG
IP 1:100

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting, IP=Immunoprecipitation,

Specificity / Sensitivity

CLOCK (D45B10) Rabbit mAb detects endogenous levels of total CLOCK protein.

CLOCK (D45B10) Rabbit mAb兔单抗能够检测内源性的CLOCK总蛋白水平。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro462 of human CLOCK protein.

通过合成的与人源CLOCK蛋白Pro462位点相应的多肽片段去免疫动物从而制备出此单克隆抗体。

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using CLOCK (D45B10) Rabbit mAb.

使用CLOCK (D45B10) Rabbit mAb兔单抗,免疫印迹(Western blot)分析不同细胞系中CLOCK蛋白。

Background

Circadian rhythms govern many key physiological processes that fluctuate with a period of approximately 24 hours. These processes include the sleep-wake cycle, glucose, lipid and drug metabolism, heart rate, hormone secretion, renal blood flow, and body temperature, as well as basic cellular processes such as DNA repair and the timing of the cell division cycle (1,2). The mammalian circadian system consists of many individual tissue-specific clocks (peripheral clocks) that are controlled by a master circadian pacemaker residing in the suprachiasmatic nuclei (SCN) of the brain (1,2). The periodic circadian rhythm is prominently manifested by the light-dark cycle, which is sensed by the visual system and processed by the SCN. The SCN processes the light-dark information and synchronizes peripheral clocks through neural and humoral output signals (1,2). 
 
 The cellular circadian clockwork consists of interwoven positive and negative regulatory loops, or limbs (1,2). The positive limb includes the CLOCK and BMAL1 proteins, two basic helix-loop-helix-PAS containing transcription factors that bind E box enhancer elements and activate transcription of their target genes. CLOCK is a histone acetyltransferase (HAT) protein, which acetylates both histone H3 and H4 (3). BMAL1 binds to CLOCK and enhances its HAT activity (3). The CLOCK/BMAL1 dimer exhibits a periodic oscillation in both nuclear/cytoplasmic localization and protein levels, both of which are regulated by phosphorylation (4,5). CLOCK/BMAL1 target genes include the Cry and Per genes, whose proteins form the negative limb of the circadian clockwork system (1,2). CRY and PER proteins (CRY1, CRY2, PER1, PER2 and PER3) form oligomers that also periodically shuttle between the nucleus and cytoplasm. When in the nucleus, CRY/PER proteins inhibit CLOCK/BMAL1-mediated transcriptional activation, thus completing the circadian transcriptional loop (1,2). In tissues, roughly six to eight percent of all genes exhibit a circadian expression pattern (1,2). This 24-hour periodicity in gene expression results from coordination of the positive and negative regulatory limbs of the cellular clockwork system, and is fine-tuned by outside signals received from the SCN.

昼夜节律调控许多关键的生理过程,其大约24小时内波动。这些过程包含觉醒周期、血糖、血脂和药物代谢、心率、激素分泌、肾血流量和体温,以及基本的细胞内过程例如DNA修复和细胞分裂周期的时间(1,2)。哺乳动物的生理系统由许多独立的组织特异生物钟(外周生物钟)组成,这些通过位于大脑视交叉上核(SCN)的主要的昼夜起搏器控制(1,2)。该周期性的昼夜节律主要的通过明暗周期证明,该明暗周期的敏感是通过视觉系统,并且通过SCN处理。SCN处理敏感周期信息和通过神经体液输出信号协调外周生物钟(1,2)。细胞内昼夜生物钟由正性和负性调控的循环或分支互相编织组成的(1,2)。负反馈环路包括CLOCK和BMAL1蛋白、两个basic helix-loop-helix-PAS家族中转录因子,这些转录因子结合E box增强元件并且激活它们的靶基因转录。CLOCK是一个组蛋白乙酰转移酶(HAT),它能催化histone H3和H4 (3)。BMAL1蛋白结合到CLOCK并且提高它的HAT活性(3)。CLOCK/BMAL1二聚体在细胞核/细胞质定位和蛋白水平中展示周期性振荡,这些都是通过磷酸化调节(4,5)。CLOCK/BMAL1靶基因包含Cry和Per基因,这些基因的蛋白形成昼夜生物钟系统的负反馈环路(1,2)。CRY和PER蛋白(CRY1、CRY2、PER1、PER2和PER3)形成低聚物,该低聚物也周期性穿梭在细胞核和细胞质中。当在细胞核中,CRY/PER蛋白抑制CLOCK/BMAL1介导的转录激活,因此完成了昼夜转录环路(1,2)。在组织中,大约百分之六到八的基因展示一个昼夜表达式模式 (1,2)。在基因表达中24小时周期是由细胞内生物钟系统的正性和负性调节环路的协调引起的,并且来自SCN的外部信号接收进行微调。

  1. Albrecht, U. and Eichele, G. (2003) Curr Opin Genet Dev 13, 271-7.
  2. Virshup, D.M. et al. (2007) Cold Spring Harb Symp Quant Biol 72, 413-20.
  3. Doi, M. et al. (2006) Cell 125, 497-508.
  4. Kondratov, R.V. et al. (2003) Genes Dev 17, 1921-32.
  5. Kwon, I. et al. (2006) Mol Cell Biol 26, 7318-30.

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Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

Cell Signaling Technology® is a trademark of Cell Signaling Technology, Inc.

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