TY - JOUR
T1 - cAMP-dependent signaling as a core component of the mammalian circadian pacemaker
AU - O'Neill, John S.
AU - Maywood, Elizabeth S.
AU - Chesham, Johanna E.
AU - Takahashi, Joseph S.
AU - Hastings, Michael H.
PY - 2008/5/16
Y1 - 2008/5/16
N2 - The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3′,5′-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.
AB - The mammalian circadian clockwork is modeled as transcriptional and posttranslational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3′,5′-monophosphate (cAMP) signaling constitutes an additional, bona fide component of the oscillatory network. cAMP signaling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase, and period. This role is general and is evident in peripheral mammalian tissues and cell lines, which reveals an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.
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U2 - 10.1126/science.1152506
DO - 10.1126/science.1152506
M3 - Article
C2 - 18487196
AN - SCOPUS:44249094901
SN - 0036-8075
VL - 320
SP - 949
EP - 953
JO - Science
JF - Science
IS - 5878
ER -