Regulation of CLOCK and MOP4 哺乳动物外周昼夜节律控制.pdf

Cell, Vol. 105, 877–889, June 29, 2001, Copyright 2001 by Cell Press Regulation of CLOCK and MOP4 by Nuclear Hormone Receptors in the Vasculature: A Humoral Mechanism to Reset a Peripheral Clock Peter McNamara,1 Sang-beom Seo,2 quently, complexes of mPER and mCRY proteins enter Radu Daniel Rudic,1 Amita Sehgal,3 the nucleus, where they shut off CLOCK:BMAL1- Debabrata Chakravarti,2 mediated transcription. At the same time, mPER2 up- and Garret A. FitzGerald1,2,4 regulates levels of Bmal1 RNA through an as yet unchar- 1Center For Experimental Therapeutics acterized mechanism leading to the formation of 2 Department of Pharmacology CLOCK:BMAL1 heterodimers which drive mPer/mCry 3 Howard Hughes Medical Institute and transcription and restart the cycle (Kume et al., 1999; Department of Neuroscience Shearman et al., 2000). MOP4 (also termed NPAS2) University of Pennsylvania School of Medicine shares high homology at the amino acid level with Philadelphia, Pennsylvania 19104 CLOCK (Hogenesch et al., 1997; Zhou et al., 1997) and like CLOCK, forms heterodimers with BMAL1 (Hogen- esch et al., 1998), promotes E box activation of genes Summary such as Per1 and vasopressin, and is negatively regu- lated by CRY1 and CRY2 (Kume et al., 1999). However, Circadian clock genes