Cooperative interaction among BMAL1, HSF1, and p53 protects mammalian cells from UV stress

Kawamura, Genki; Hattori, Mitsuru; Takamatsu, Ken; Tsukada, Teruyo; Ninomiya, Yasuharu; Benjamin, Ivor J.; Sassone–Corsi, Paolo; Ozawa, Toshio; Tamaru, Teruya

doi:10.1038/s42003-018-0209-1

Cited by 28 publications

(17 citation statements)

References 44 publications

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“…HSF1 is induced upon cell stressors such as UV light, oxidative stress and heat stress, and triggers the synchronization of the circadian clock via directly regulating the core clock gene Per2 [45,46,47]. According to the HSF1Base, some of the putative HSF1 targets associated with the circadian rhythm are upregulated ( RXRA , NOCT , BHLHE40 , SERPINE1, and DBP ) while others are inhibited ( NCOA2 , ARNTL, and TBL1X ) by the transcription factor (Figure 2D, Table 2 and Table S6).…”

Section: Discussionmentioning

confidence: 99%

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

Kovács

Sigmond

Hotzi

et al. 2019

IJMS

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HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist the refolding or degradation of damaged intracellular proteins. Accumulating evidence reveals however that HSF1 participates in several other physiological and pathological processes such as differentiation, immune response, and multidrug resistance, as well as in ageing, neurodegenerative demise, and cancer. To address how HSF1 controls these processes one should systematically analyze its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analyzing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and the Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodeling, ribosome biogenesis, and ageing. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR.

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Section: Discussionmentioning

confidence: 99%

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

Kovács

Sigmond

Hotzi

et al. 2019

IJMS

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“…The circadian CLOCK interacts with BMAL1, and heat shock factor-1 (HSF1) during heat stress and oxidative stress was previously reported (Tamaru et al, 2011). In addition, the CLOCK system also controls the expression of stress resistance genes (i.e., PER2 and BMAL1) (Zhang et al, 2014) and activates various adaptive protection pathways that control antioxidant and cell survival responses to protect cells from stressors (Kawamura et al, 2018). In summary, the ARNTL gene was identified in heat-stressed rats and cattle and also functions as an important biomarker for several diseases in humans (Engin, 2017;Maiese, 2017).…”

Section: Cross-species Analysis Of Candidate Genesmentioning

confidence: 95%

Comprehensive RNA-Seq Profiling Reveals Temporal and Tissue-Specific Changes in Gene Expression in Sprague–Dawley Rats as Response to Heat Stress Challenges

et al. 2021

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Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague–Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood (P < 0.05 and |fold change (FC)| >2), liver (P < 0.01, false discovery rate (FDR)–adjusted P = 0.05 and |FC| >2) and adrenal glands (P < 0.01, FDR-adjusted P = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely Junb, P4ha1, Chordc1, and RT1-Bb, were shared among the three tissues in CT vs. H120 comparison. Functional enrichment analyses of the DEGs identified in the blood (CT vs. H120) revealed 12 biological processes (BPs) and 25 metabolic pathways significantly enriched (FDR = 0.05). In the liver, 133 BPs and three metabolic pathways were significantly detected by comparing CT vs. H30, H60, and H120. Furthermore, 237 BPs were significantly (FDR = 0.05) enriched in the adrenal glands, and no shared metabolic pathways were detected among the different heat-stressed groups of rats. Five and four expression patterns (P < 0.05) were uncovered by 73 and 91 shared DEGs in the liver and adrenal glands, respectively, over the different comparisons. Among these, 69 and 73 genes, respectively, were proposed as candidates for regulating heat stress response in rats. Finally, together with genome-wide association study (GWAS) results in cattle and phenome-wide association studies (PheWAS) analysis in humans, five genes (Slco1b2, Clu, Arntl, Fads1, and Npas2) were considered as being associated with heat stress response across mammal species. The datasets and findings of this study will contribute to a better understanding of heat stress response in mammals and to the development of effective approaches to mitigate heat stress response in livestock through breeding.

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“…For the ubiquitin-independent pathways the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) has been indicated to have a major regulatory role [41,42]. In unstressed cells there is further evidence that p53 and the circadian clock [30] undergo cooperative regulations [43–46] via the Per2 protein. Per2 is not only an important component of the human circadian oscillator [47], but also takes part in the input and output pathways of the clock [48].…”

Section: Resultsmentioning

confidence: 99%

Frequency switching between oscillatory homeostats and the regulation of p53

Ruoff

Nishiyama

2020

Preprint

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1Homeostasis is an essential concept to understand the stability of organisms and their 2 adaptive behaviors when coping with external and internal assaults. Many hormones 3 that take part in homeostatic control come in antagonistic pairs, such as glucagon and 4 insulin reflecting the inflow and outflow compensatory mechanisms to control a certain 5 internal variable, such as blood sugar levels. By including negative feedback loops 6 homeostatic controllers can exhibit oscillations with characteristic frequencies. In this 7 paper we demonstrate the associated frequency changes in homeostatic systems when 8 individual controllers in a set of interlocked feedback loops gain control in response to 9 environmental changes. Taking p53 as an example, we show how the Per2, ATM and 10 Mdm2 feedback loops -interlocked with p53-gain individual control in dependence to 11 DNA damage and how each of these controllers provide certain functionalities in their 12 regulation of p53. In unstressed cells, the circadian regulator Per2 ensures a basic p53 13 level to allow its rapid up-regulation in case of DNA damage. When DNA damage 14 occurs the ATM controller increases the level of p53 and defends it towards uncontrolled 15 degradation, which despite DNA damage, would drive p53 to lower values and p53 16dysfunction. Mdm2 on its side keeps p53 at a maximum level to avoid premature 17 apoptosis. However, with on-going DNA damage the Mdm2 set-point is increased by 18 HSP90 and other p53 stabilizers leading finally to apoptosis. An essential aspect in p53 19 regulation at occurring cell stress is the coordinated inhibition of ubiquitin-independent 20 and ubiquitin-dependent degradation reactions and the increasing stabilizing 21 mechanisms of p53. Whether oscillations serve a function or are merely a by-product of 22 the controllers are discussed in view of the finding that homeostatic control of p53, as 23 indicated above, does in principle not require oscillatory homeostats. 24 30 control [8], alongside with integral feedback [9][10][11], and systems biology methods [12, 13]. 31 It became clear that certain reaction kinetic conditions are necessary for the occurrence 32December 24, 2019 1/17 of integral control leading to the robustness of the feedback controller. These conditions 33 include zero-order kinetics [9, 10,[14][15][16][17][18][19], autocatalysis [20][21][22], and second-order 34 (bimolecular/antithetic) reaction [23, 24], which were implemented into various controller 35 motifs, synthetic gene networks, and other negative feedback structures [18,[25][26][27]. 36A particular interesting aspect is that, under certain conditions, the homeostatic 37 controllers may become oscillatory and preserve, if integral control is present, their 38 homeostatic property by keeping the average value of the controlled variable at its 39 set-point [28]. While the occurrence of oscillations is generally avoided in control 40 engineering, natural systems show generally oscillatory behaviors, as found in circadian 41 or ultradian rhythms ...

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Cooperative interaction among BMAL1, HSF1, and p53 protects mammalian cells from UV stress

Cited by 28 publications

References 44 publications

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes

Comprehensive RNA-Seq Profiling Reveals Temporal and Tissue-Specific Changes in Gene Expression in Sprague–Dawley Rats as Response to Heat Stress Challenges

Frequency switching between oscillatory homeostats and the regulation of p53

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