The mammalian circadian clock protein period counteracts cryptochrome in
phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK)
#MMPMID25271155
Matsumura R
; Tsuchiya Y
; Tokuda I
; Matsuo T
; Sato M
; Node K
; Nishida E
; Akashi M
J Biol Chem
2014[Nov]; 289
(46
): 32064-32072
PMID25271155
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The circadian transcription factor CLOCK exhibits a circadian oscillation in its
phosphorylation levels. Although it remains unclear whether this phosphorylation
contributes to circadian rhythm generation, it has been suggested to be involved
in transcriptional activity, intracellular localization, and degradative turnover
of CLOCK. Here, we obtained direct evidence that CLOCK phosphorylation may be
essential for autonomous circadian oscillation in clock gene expression.
Importantly, we found that the circadian transcriptional repressors Cryptochrome
(CRY) and Period (PER) showed an opposite effect on CLOCK phosphorylation; CRY
impaired BMAL1-dependent CLOCK phosphorylation, whereas PER protected the
phosphorylation against CRY. Interestingly, unlike PER1 and PER2, PER3 did not
exert a protective action, which correlates with the phenotypic differences among
mice lacking the Per genes. Further studies on the regulatory mechanism of CLOCK
phosphorylation would thus lead to elucidation of the mechanism of CRY-mediated
transcriptional repression and an understanding of the true role of PER in the
negative feedback system.
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