1. CIPC is a mammalian circadian clock protein without invertebrate homologues
- Author
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Wen-Ning Zhao, Nikolay Malinin, Fu-Chia Yang, Charles J. Weitz, Silke Reischl, Nicholas Gekakis, Achim Kramer, Bert Maier, and David Staknis
- Subjects
Transcriptional Activation ,Circadian clock ,Regulator ,CLOCK Proteins ,Cell Cycle Proteins ,Endogeny ,Biology ,Kidney ,Transfection ,Mice ,Cryptochrome ,Biological Clocks ,Two-Hybrid System Techniques ,Negative feedback ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Immunoprecipitation ,RNA, Antisense ,Circadian rhythm ,Transcription factor ,Gene ,Cell Nucleus ,Mammals ,Flavoproteins ,Myocardium ,ARNTL Transcription Factors ,Nuclear Proteins ,Period Circadian Proteins ,Cell Biology ,Peptide Fragments ,Circadian Rhythm ,Cell biology ,Cryptochromes ,Mice, Inbred C57BL ,Gene Expression Regulation ,Liver ,Mutation ,NIH 3T3 Cells ,Trans-Activators ,Carrier Proteins ,Protein Binding - Abstract
At the core of the mammalian circadian clock is a feedback loop in which the heterodimeric transcription factor CLOCK-Brain, Muscle Arnt-like-1 (BMAL1) drives expression of its negative regulators, periods (PERs) and cryptochromes (CRYs). Here, we provide evidence that CLOCK-Interacting Protein, Circadian (CIPC) is an additional negative-feedback regulator of the circadian clock. CIPC exhibits circadian regulation in multiple tissues, and it is a potent and specific inhibitor of CLOCK-BMAL1 activity that functions independently of CRYs. CIPC-CLOCK protein complexes are present in vivo, and depletion of endogenous CIPC shortens the circadian period length. CIPC is unrelated to known proteins and has no recognizable homologues outside vertebrates. Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks.
- Published
- 2007
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