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J. Biochem, 2003, Vol. 134, No. 6 777-784
© 2003 Japanese Biochemical Society

JB SPECIAL REVIEWS

Molecular Mechanism of Mammalian Circadian Clock

Yasushi Isojima, Nobuaki Okumura and Katsuya Nagai*

Division of Protein Metabolism, Institute for Protein Research, Osaka University, 3-2, Yamada-oka, Suita-ku, Osaka 565-0871

ABSTRACT

Circadian rhythms in behaviors and physiological phenomena of plants and animals have long been well known, but the frameworks of the molecular mechanism of circadian clocks have become clearer only within the last decade. A transcription-translation feedback loop has been shown to be an essential component of the clock, and this mechanism seems to be conserved over a wide range of species. The transcriptional activation by a Clock:Bmal1 heterodimer and the inhibition by Cryptochrome and Period are believed to provide the framework of the feedback loop in mammals. Posttranslational modifications such as phosphorylation, nuclear entry and degradation have also been demonstrated to be necessary for the oscillation. Complex auxiliary loops have also been found, and these are thought to contribute to the stabilization of the feedback loop. The molecular mechanisms by which the circadian clock is adjusted to external conditions such as daily light-dark cycles, and by which the oscillation of the feedback loop is transferred to the peripheral organs are also discussed.

FOOTNOTES

* To whom correspondence should be addressed. Tel: +81-6-6879-8632, Fax: +81-6-6879-8633, E-mail: k_nagai{at}protein.osaka-u.ac.jp


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