Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock

Dang, Fabin; Sun, Xiujie; Ma, Xiang; Wu, Rong; Zhang, Deyi; Chen, Yaqiong; Qian, Xu; Wu, Yuting; Liu, Yi

doi:10.1038/ncomms12696

Cited by 104 publications

(73 citation statements)

References 45 publications

(75 reference statements)

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“…2E). Consistent with our data, with less protein amounts, BMAL1-S42A bound to E-box elements in the promoters of both Dbp and Nr1d1 is substantially higher than WT BMAL1, and mRNA levels of these two genes are enhanced by the BMAL1 mutation in liver (70). Another possibility is that PKA could directly phosphorylate UBE3A at T485 and inhibit UBE3A ubiquitin ligase activity (71).…”

Section: Discussionsupporting

confidence: 90%

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

Zhang

Qin

Feng

et al. 2019

Preprint

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At the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-Cα by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-Cα induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.

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Section: Discussionsupporting

confidence: 90%

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

Zhang

Qin

Feng

et al. 2019

Preprint

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“…Under this circumstance, the effect of BMAL1 on MMPs was compromised. The results suggested that BMAL1 might serve as a transcription factor or interact with other transcription factors to regulate MMPs expression, as BMAL1 has actively been implicated in NF‐κB signaling and Akt signaling transduction [Dang et al, ; Spengler et al, ; Garcia et al, ]. Other studies also have reported the role of BMAL1 in regulating MMPs expression using BMAL1 knockout model [Anea et al, ].…”

Section: Discussionmentioning

confidence: 96%

Activation of MMPs in Macrophages by Mycobacterium tuberculosis via the miR‐223‐BMAL1 Signaling Pathway

Lou

Wang

Zhang

et al. 2017

J of Cellular Biochemistry

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An interaction between Mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on M. tuberculosis-triggered organ lesions. In this study, we focused on the regulation of the expression of matrix metalloproteinases (MMPs), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following M. tuberculosis infection. Female BALB/c mice were intravenously injected with the M. tuberculosis strain H37Rv at 0 h zeitgeber time (ZT0) or 12 h zeitgeber time (ZT12). The expression and activity of MMP-1, -2, -3, and -9 in lungs and spleens were then evaluated. In vitro, peritoneal macrophages were harvested at ZT0 or at ZT12 and infected with 10 MOI M. tuberculosis. The expression of MMPs, microRNA-223 and BMAL1 was analyzed by qRT-PCR and/or Western blot. The binding of BMAL1 3'-UTR by miR-223 was confirmed by luciferase activity assay. Additionally, wild-type BMAL1 or NLS BMAL1 plasmids were transfected to evaluate the effect of BMAL1 on MMPs. The results showed a differential expression of MMPs in mice tissues infected at different times. M. tuberculosis infection caused enhanced MMP-1, -9, and miR-223 expression, with inhibited BMAL1 expression. MiR-223 modulated BMAL1 expression via the direct binding of BMAL1 3'-UTR. Furthermore, wild-type BMAL1 other than NLS BMAL1 attenuated MMPs expression in M. tuberculosis-infected macrophages. Overall, this study demonstrated a potential involvement of circadian rhythm in MMP activation by M. tuberculosis in macrophages. J. Cell. Biochem. 118: 4804-4812, 2017. © 2017 Wiley Periodicals, Inc.

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“…AKT or S6K1 also phosphorylates BMAL1 and recruits it to translation complexes, where it promotes complex activity ( Fig. 2E) (45,46). In combination with circadian rhythms in ribosome biogenesis (47) and preferential translation of specific subsets of mRNAs (48), this general rhythm in protein synthesis is specifically important for liver function, because it is a major source of critical secreted proteins, including albumin, retinol-binding pro-tein, transthyretin, and proteins of the complement pathway.…”

Section: Proteinmentioning

confidence: 99%

Circadian physiology of metabolism

Panda

2016

Science

743

586

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A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark.

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Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock

Cited by 104 publications

References 45 publications

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

Activation of MMPs in Macrophages by Mycobacterium tuberculosis via the miR‐223‐BMAL1 Signaling Pathway

Circadian physiology of metabolism

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