Abstract
Circadian rhythm is an autoregulatory rhythm, which is sustained by various mechanisms. The nucleocytoplasmic shuttling of BMAL1 is essential for CLOCK translocation between cytoplasm and nucleus and maintenance of the correct pace of the circadian clock. Here we showed that RAE1 and NUP98 can promote the degradation of BMAL1 and CLOCK. Knockdown of RAE1 and NUP98 suppressed BMAL1 shuttling, leading to cytoplasm accumulation of CLOCK. Furthermore, Chip assay showed that knockdown of RAE1 and NUP98 can enhance the interaction between CLOCK: BMAL1 and E-box region in the promoters of Per2 and Cry1 while reducing its transcription activation activity. Our present study firstly revealed that RAE1 and NUP98 are critical regulators for BMAL1 shuttling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ARNTL Transcription Factors / metabolism*
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Animals
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CLOCK Proteins / metabolism*
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Circadian Clocks / physiology
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Circadian Rhythm / physiology
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Gene Knockdown Techniques
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HEK293 Cells
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Humans
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Mice
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NIH 3T3 Cells
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Nuclear Matrix-Associated Proteins / genetics
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Nuclear Matrix-Associated Proteins / metabolism*
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Nuclear Pore Complex Proteins / genetics
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Nuclear Pore Complex Proteins / metabolism*
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Nucleocytoplasmic Transport Proteins / genetics
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Nucleocytoplasmic Transport Proteins / metabolism*
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Plasmids / genetics
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Protein Multimerization*
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Proteolysis*
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Transcriptional Activation / genetics
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Transfection
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Ubiquitination / genetics
Substances
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ARNTL Transcription Factors
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BMAL1 protein, human
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Bmal1 protein, mouse
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Nuclear Matrix-Associated Proteins
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Nuclear Pore Complex Proteins
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Nucleocytoplasmic Transport Proteins
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RAE1 protein, human
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Rae1 protein, mouse
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nuclear pore complex protein 98
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CLOCK Proteins
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CLOCK protein, human
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Clock protein, mouse