JNK regulates the photic response of the mammalian circadian clock.
Summary of "JNK regulates the photic response of the mammalian circadian clock."
The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light.
Affiliation
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
Journal Details
This article was published in the following journal.
Name: EMBO reports
ISSN: 1469-3178
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22441692
- DOI: http://dx.doi.org/10.1038/embor.2012.37
Medical and Biotech [MESH] Definitions
Period Circadian Proteins
Circadian rhythm signaling proteins that influence circadian clock by interacting with other circadian regulatory proteins and transporting them into the CELL NUCLEUS.
Clock Proteins
Basic helix-loop-helix (bHLH) domain-containing proteins that contain intrinsic HISTONE ACETYLTRANSFERASE activity and play important roles in CIRCADIAN RHYTHM regulation. Clock proteins combine with Arntl proteins to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation. This transcriptional activation also sets into motion a time-dependent feedback loop which in turn down-regulates the expression of clock proteins.
Nuclear Receptor Subfamily 1, Group D, Member 1
A DNA-binding orphan nuclear receptor that negatively regulates expression of ARNTL TRANSCRIPTION FACTORS and plays a role as a regulatory component of the circadian clock system. The Nr1d1 nuclear receptor expression is cyclically-regulated by a feedback loop involving its positive regulation by CLOCK PROTEIN; BMAL1 PROTEIN heterodimers and its negative regulation by CRYPTOCHROME and PERIOD PROTEINS.
Nuclear Receptor Subfamily 1, Group F, Member 1
A DNA-binding orphan nuclear receptor that positively regulates expression of ARNTL TRANSCRIPTION FACTORS and is a regulatory component of the circadian clock system. The protein also has a role in neuron cell survival and differentiation in that loss of function mutations of its gene result in the mouse phenotype referred to as the STAGGERER MOUSE.
Circadian Rhythm
The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness.
PubMed Articles
Timing of the mammalian circadian clock of the suprachiasmatic nucleus (SCN) is regulated by photic input from the retina. Retinorecipient units entrain rhythmicity of SCN pacemaker cells in part thro...
MicroRNA-mediated regulation in the mammalian circadian rhythm.
Mammalian circadian rhythms have been extensively studied for many years and many computational models have been presented. Most of the circadian rhythms are based on interlocked positive and negative...
Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock.
In animals, circadian oscillators are based on a transcription-translation circuit that revolves around the transcription factors CLOCK and BMAL1. We found that the JumonjiC (JmjC) and ARID domain-con...
The circadian clock, an endogenous timekeeper that regulates daily rhythms of physiology, also influences the dynamic release of glucocorticoids. The release of glucocorticoids is characteristically p...
Perfect timing: Epigenetic regulation of the circadian clock.
In mammals, higher order chromatin structures are critical for downsizing the genome (packaging) so that the nucleus can be small. The adjustable density of chromatin also regulates gene expression, t...
Clinical Trials
Bright Light as a Countermeasure for Circadian Desynchrony
Light is the primary means by which the internal circadian clock remains aligned ("entrained") with the external world. Misalignment of this internal clock can occur during situations suc...
Pilot Study of the Effects of Circadian Rhythms on the Treatment of Bipolar I Depression.
The objective of this pilot study is to test the feasibility of a larger planned trial. The objective of this larger trial will be to determine the extent to which aspects of circadian rhy...
Ambulatory Anesthesia and Light Therapy
We previously evidenced in both animal models and patients that a short duration ambulatory anesthesia impacts the circadian rest-activity biological rhythm, at least during the first 3...
Sleep Length and Circadian Regulation in Humans
This research will examine why sleep restriction reduces the body clock's response to bright light. The results will enable the optimization of the bright light treatment of people who suf...
Circadian Regulation of Sleep in Habitual Short Sleepers and Long Sleepers
Routine sleep duration varies greatly among individuals. The biological meaning of this variation is unknown. The term circadian rhythm refers to the biological clock that regulates the...
