Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/77783
Title: REGULATION OF CASEIN KINASE 1 IN CIRCADIAN RYTHMS
Authors: ENG WEE LING
Keywords: Casein Kinase 1, Circadian rhythms, Period degradation, Phosphorylation
Issue Date: 23-Jan-2014
Source: ENG WEE LING (2014-01-23). REGULATION OF CASEIN KINASE 1 IN CIRCADIAN RYTHMS. ScholarBank@NUS Repository.
Abstract: Background: Casein kinase 1 delta/epsilon (CK1d/e) are key regulators of circadian rhythms. They phosphorylate Period (Per), regulating their cellular localization and degradation. Per levels in cells oscillate in a 24-hour rhythm. Whether CK1d/e activity also oscillates in a circadian manner to regulate Per is still unknown. CK1d/e had been shown to autophosphorylate themselves on their carboxy-terminal tail to result in inhibition of their kinase activity. Phosphorylation is thus a possible mechanism for regulating kinase activity throughout the circadian cycle. Results: Our data implied that CK1d/e?s activity changes over time, thereby targeting Per for degradation in a circadian fashion. I find circadian changes in the phosphorylation of CK1d/e. I generated a constitutively active mutant CK1d lacking all reported phosphorylation sites. This mutation showed increased activity on Per2 degradation. I subsequently identified specific residues as potential regulatory sites on CK1d that affects Per2 homeostasis. Conclusion: Regulation of CK1d plays a role on Per2 stability and may have an impact on the regulation of circadian rhythms. Future work will focus on characterizing these regulatory sites and their effects on rhythms in vivo.
URI: http://scholarbank.nus.edu.sg/handle/10635/77783
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01Chap1&2 EngWL.pdf2.65 MBAdobe PDF

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02Results1 EngWL.pdf9.35 MBAdobe PDF

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03Results2 EngWL.pdf3.78 MBAdobe PDF

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04Results3 & Discussions EngWL.pdf19.07 MBAdobe PDF

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05Ref & Appendices EngWL.pdf574.04 kBAdobe PDF

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