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Pathway Description
Circadian Rhythms
Homo sapiens
Category:
Protein Pathway
Sub-Categories:
Gene Regulatory
Kinase Signaling
Created: 2018-08-15
Last Updated: 2019-08-16
The nuclear entry of clock gene products is required to establish the negative feed back loop- a key step in proper circadian rhythm. Heterodimerization of clock proteins PER and CRY is required for translocation to the nucleus. Nuclear entry of PER can be regulated by mammalian casein kinase I (CK1). Once in the nucleus, PER and CRY proteins appear to differentially inhibit the transactivation by CLOCK/BMAL1. Proteins like REV-ERBa and DEC also regulate the transcriptional activation by CLOCK/BMAL1. In addition, CRY, PER, and BMAL1-CLOCK play bidirectional roles in transcription resulting in interactivating feedback loops. The expression of BMAL1 and CLOCK can be upregulated by CRY and PER. Such loops are believed to be important in the stability and persistence of circadian rhythm.
References
Circadian Rhythms References
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Rong-ChiHuang. (2018) The discoveries of molecular mechanisms for the circadian rhythm: The 2017 Nobel Prize in Physiology or Medicine. Biomedical Journal, Volume 41, Issue 1, February 2018, Pages 5-8
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Steeves TD, King DP, Zhao Y, Sangoram AM, Du F, Bowcock AM, Moore RY, Takahashi JS: Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei. Genomics. 1999 Apr 15;57(2):189-200. doi: 10.1006/geno.1998.5675.
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Li R, Yue J, Zhang Y, Zhou L, Hao W, Yuan J, Qiang B, Ding JM, Peng X, Cao JM: CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter. Mol Cell Biochem. 2008 Oct;317(1-2):169-77. doi: 10.1007/s11010-008-9846-x. Epub 2008 Jun 28.
Pubmed: 18587630
Ward SM, Fernando SJ, Hou TY, Duffield GE: The transcriptional repressor ID2 can interact with the canonical clock components CLOCK and BMAL1 and mediate inhibitory effects on mPer1 expression. J Biol Chem. 2010 Dec 10;285(50):38987-9000. doi: 10.1074/jbc.M110.175182. Epub 2010 Sep 22.
Pubmed: 20861012
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