scholarly journals Ubiquitin ligase TRAF 2 attenuates the transcriptional activity of the core clock protein BMAL 1 and affects the maximal Per1 mRNA level of the circadian clock in cells

FEBS Journal ◽  
2018 ◽  
Vol 285 (16) ◽  
pp. 2987-3001 ◽  
Author(s):  
Suping Chen ◽  
Jing Yang ◽  
Lu Yang ◽  
Yang Zhang ◽  
Liang Zhou ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Ubiquitin Ligase ◽  
Transcriptional Activity ◽  
Mrna Level ◽  
The Core ◽  
Clock Protein ◽  
In Cells

scholarly journals The Resonance and Adaptation of Neurospora crassa Circadian and Conidiation Rhyth ms to Short Light-Dark Cycles

2021 ◽  
Vol 8 (1) ◽  
pp. 27
Author(s):  
Huan Ma ◽  
Luyao Li ◽  
Jie Yan ◽  
Yin Zhang ◽  
Xiaohong Ma ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Neurospora Crassa ◽  
Circadian Clocks ◽  
Extreme Conditions ◽  
Behavioral Rhythms ◽  
The Core ◽  
Regulatory Aspects ◽  
Ubiquitin E3 Ligase ◽  
Modeling And Experiments ◽  
Clock Protein

Circadian clocks control the physiological and behavioral rhythms to adapt to the environment with a period of ~24 h. However, the influences and mechanisms of the extreme light/dark cycles on the circadian clock remain unclear. We showed that, in Neurospora crassa, both the growth and the microconidia production contribute to adaptation in LD12:12 (12 h light/12 h dark, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY was entrained to the LD cycles when LD > 3:3 while it free ran when T ≤ LD3:3. The conidial rhythmicity can resonate with a series of different LD conditions. Moreover, we demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions. These findings shed new light on the resonance of Neurospora circadian clock and conidiation rhythms to short LD cycles, which may benefit the understandings of both the basic regulatory aspects of circadian clock and the adaptation of physiological rhythms to the extreme conditions.

scholarly journals Visualizing and Quantifying Intracellular Behavior and Abundance of the Core Circadian Clock Protein PERIOD2

2016 ◽  
Vol 26 (14) ◽  
pp. 1880-1886 ◽  
Author(s):  
Nicola J. Smyllie ◽  
Violetta Pilorz ◽  
James Boyd ◽  
Qing-Jun Meng ◽  
Ben Saer ◽  
...  
Keyword(s):  
Circadian Clock ◽  
The Core ◽  
Clock Protein

scholarly journals Live-cell imaging of circadian clock protein dynamics in CRISPR-generated knock-in cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christian H. Gabriel ◽  
Marta del Olmo ◽  
Amin Zehtabian ◽  
Marten Jäger ◽  
Silke Reischl ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Cell Biology ◽  
Fluorescent Proteins ◽  
Single Cells ◽  
Current Model ◽  
Clock Proteins ◽  
Low Levels ◽  
Circadian Clock Proteins ◽  
Clock Protein ◽  
In Cells

AbstractThe cell biology of circadian clocks is still in its infancy. Here, we describe an efficient strategy for generating knock-in reporter cell lines using CRISPR technology that is particularly useful for genes expressed transiently or at low levels, such as those coding for circadian clock proteins. We generated single and double knock-in cells with endogenously expressed PER2 and CRY1 fused to fluorescent proteins allowing us to simultaneously monitor the dynamics of CRY1 and PER2 proteins in live single cells. Both proteins are highly rhythmic in the nucleus of human cells with PER2 showing a much higher amplitude than CRY1. Surprisingly, CRY1 protein is nuclear at all circadian times indicating the absence of circadian gating of nuclear import. Furthermore, in the nucleus of individual cells CRY1 abundance rhythms are phase-delayed (~5 hours), and CRY1 levels are much higher (>5 times) compared to PER2 questioning the current model of the circadian oscillator.

scholarly journals Cell-autonomous regulation of astrocyte activation by the circadian clock protein BMAL1

2018 ◽  
Author(s):  
Brian V. Lananna ◽  
Collin J. Nadarajah ◽  
Mariko Izumo ◽  
Michelle R. Cedeño ◽  
David D. Xiong ◽  
...  
Keyword(s):  
Circadian Clock ◽  
List Type ◽  
Brain Health ◽  
Glutathione S Transferase ◽  
Astrocyte Activation ◽  
The Core ◽  
A Cell ◽  
Clock Protein

SummaryCircadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.HighlightsCircadian disruption promotes astrocyte activation.Astrocyte-specific deletion of the circadian clock gene BMAL1 induces astrocyte activation.BMAL1 regulates astrocyte activation by altering glutathione-s-transferase signaling.Loss of astrocyte BMAL1 enhances neuronal cell death in a co-culture system.eTOC blurbLananna et al. show that the circadian clock protein BMAL1 regulates astrocyte activation via a cell autonomous-mechanism involving diminished glutathione-s-transferase signaling. This finding elucidates a novel function of the core circadian clock in astrocytes, and reveals a BMAL1 as a modulator of astrogliosis.

Deubiquitinating enzyme USP9X regulates cellular clock function by modulating the ubiquitination and degradation of a core circadian protein BMAL1

2018 ◽  
Vol 475 (8) ◽  
pp. 1507-1522 ◽  
Author(s):  
Yang Zhang ◽  
Chunyan Duan ◽  
Jing Yang ◽  
Suping Chen ◽  
Qing Liu ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Affinity Purification ◽  
Mass Spectrometry Analysis ◽  
Regulatory Function ◽  
Spectrometry Analysis ◽  
The Core ◽  
Clock Proteins ◽  
Clock Protein

Living organisms on the earth maintain a roughly 24 h circadian rhythm, which is regulated by circadian clock genes and their protein products. Post-translational modifications of core clock proteins could affect the circadian behavior. Although ubiquitination of core clock proteins was studied extensively, the reverse process, deubiquitination, has only begun to unfold and the role of this regulation on circadian function is not completely understood. Here, we use affinity purification and mass spectrometry analysis to identify probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) as an interacting protein of the core clock protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1). Through biochemical experiments, we discover that USP9X reduces BMAL1 ubiquitination, enhances its stability, and increases its protein level, leading to the elevated transcriptional activity. Bioluminescence measurement reveals that USP9X knockdown decreases the amplitude of the cellular circadian rhythm but the period and phase are not affected. Our experiments find a new regulator for circadian clock at the post-translational level and demonstrate a different regulatory function for the circadian clock through the deubiquitination and the up-regulation of the core clock protein BMAL1 in the positive limb of the transcription–translation feedback loop.

scholarly journals The synchronization and adaptation of Neurospora crassa circadian and conidiation rhythms to short light-dark cycles

2018 ◽  
Author(s):  
Huan Ma ◽  
Luyao Li ◽  
Jie Yan ◽  
Yin Zhang ◽  
Weirui Shi ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Neurospora Crassa ◽  
Metabolic Pathways ◽  
Diurnal Rhythms ◽  
Daily Rhythms ◽  
The Core ◽  
Ubiquitin E3 Ligase ◽  
Modeling And Experiments ◽  
High Intensity Light ◽  
Clock Protein

ABSTRACTCircadian clocks control the physiological and behavioral daily rhythms to adapt to the changing environment with a period of ~24 h. However, the influence and mechanism of extreme light-dark cycles on the circadian clock remain unclear. We show that, in the fungus Neurospora crassa under short LD cycles, both the growth rate and the ratio of microconidia production contributes to adaptation in LD12:12 (light for 12 h and dark for 12 h, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY is entrained to the LD cycles when LD>3:3 while it free runs when T≤ LD3:3. We investigated the changes in circadian/diurnal rhythms under a series of different LD conditions, and the results showed that conidial rhythmicity can be adapted to the short LD cycles. We further demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. A high-intensity light induced the expression of a set of downstream genes involved in various metabolic pathways. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions.

scholarly journals Selenium is a modulator of circadian clock that protects mice from the toxicity of a chemotherapeutic drug via upregulation of the core clock protein, BMAL1

Oncotarget ◽  
2011 ◽  
Vol 2 (12) ◽  
pp. 1279-1290 ◽  
Author(s):  
Yan Hu ◽  
Mary L. Spengler ◽  
Karen K. Kuropatwinski ◽  
Maria Comas-Soberats ◽  
Marilyn Jackson ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Chemotherapeutic Drug ◽  
The Core ◽  
Clock Protein
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