scholarly journals HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans

2019 ◽  
Author(s):  
Surojit Sural ◽  
Tzu-Chiao Lu ◽  
Seung Ah Jung ◽  
Ao-Lin Hsu
Keyword(s):  
Heat Shock ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Heat Shock Factor ◽  
Binding Activity ◽  
Negative Regulator ◽  
Target Sequence ◽  
Heat Shock Factor 1 ◽  
Altered Expression ◽  
Genetic Ablation

ABSTRACTHeat shock factor 1 (HSF-1) is a component of the heat shock response pathway that is induced by cytoplasmic proteotoxic stress. In addition to its role in stress response, HSF-1 also acts as a key regulator of the rate of organismal aging. Overexpression of HSF-1 promotes longevity in C. elegans via mechanisms that remain less understood. Moreover, genetic ablation of a negative regulator of HSF-1, termed as heat shock factor binding protein 1 (HSB-1), results in hsf-1-dependent life span extension in animals. Here we show that in the absence of HSB-1, HSF-1 acquires increased DNA binding activity to its genomic target sequence. Using RNA-Seq to compare the gene expression profiles of the hsb-1 mutant and hsf-1 overexpression strains, we found that while more than 1,500 transcripts show ≥1.5-fold upregulation due to HSF-1 overexpression, HSB-1 inhibition alters the expression of less than 500 genes in C. elegans. Roughly half of the differentially regulated transcripts in the hsb-1 mutant have altered expression also in hsf-1 overexpressing animals, with a strongly correlated fold-expression pattern between the two strains. In addition, genes that are upregulated via both HSB-1 inhibition and HSF-1 overexpression include numerous DAF-16 targets that have known functions in longevity regulation. This study identifies how HSB-1 acts as a specific regulator of the transactivation potential of HSF-1 in non-stressed conditions, thus providing a detailed understanding of the role of HSB-1/HSF-1 signaling pathway in transcriptional regulation and longevity in C. elegans.

scholarly journals Neurospora crassa heat shock factor 1 Is an Essential Gene; a Second Heat Shock Factor-Like Gene, hsf2, Is Required for Asexual Spore Formation

2008 ◽  
Vol 7 (9) ◽  
pp. 1573-1581 ◽  
Author(s):  
Seona Thompson ◽  
Nirvana J. Croft ◽  
Antonis Sotiriou ◽  
Hugh D. Piggins ◽  
Susan K. Crosthwaite
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Neurospora Crassa ◽  
Essential Gene ◽  
Expression Profiles ◽  
Heat Shock Factor ◽  
Model Organisms ◽  
Heat Shock Factor 1 ◽  
Wild Type ◽  
Altered Expression

ABSTRACT Appropriate responses of organisms to heat stress are essential for their survival. In eukaryotes, adaptation to high temperatures is mediated by heat shock transcription factors (HSFs). HSFs regulate the expression of heat shock proteins, which function as molecular chaperones assisting in protein folding and stability. In many model organisms a great deal is known about the products of hsf genes. An important exception is the filamentous fungus and model eukaryote Neurospora crassa. Here we show that two Neurospora crassa genes whose protein products share similarity to known HSFs play different biological roles. We report that heat shock factor 1 (hsf1) is an essential gene and that hsf2 is required for asexual development. Conidiation may be blocked in the hsf2 knockout (hsf2 KO ) strain because HSF2 is an integral element of the conidiation pathway or because it affects the availability of protein chaperones. We report that genes expressed during conidiation, for example fluffy, conidiation-10, and repressor of conidiation-1 show wild-type levels of expression in a hsf2 KO strain. However, consistent with the lack of macroconidium development, levels of eas are much reduced. Cultures of the hsf2 KO strain along with two other aconidial strains, the fluffy and aconidial-2 strains, took longer than the wild type to recover from heat shock. Altered expression profiles of hsp90 and a putative hsp90-associated protein in the hsf2 KO strain after exposure to heat shock may in part account for its reduced ability to cope with heat stress.

scholarly journals HSB-1/HSF-1 pathway modulates histone H4 in mitochondria to control mtDNA transcription and longevity

2020 ◽  
Vol 6 (43) ◽  
pp. eaaz4452
Author(s):  
Surojit Sural ◽  
Chung-Yi Liang ◽  
Feng-Yung Wang ◽  
Tsui-Ting Ching ◽  
Ao-Lin Hsu
Keyword(s):  
Heat Shock ◽  
Life Span ◽  
Stress Responses ◽  
Heat Shock Factor ◽  
Negative Regulator ◽  
Micrococcal Nuclease ◽  
Heat Shock Factor 1 ◽  
Histone H4 ◽  
Life Span Extension ◽  
Genetic Ablation

Heat shock factor–1 (HSF-1) is a master regulator of stress responses across taxa. Overexpression of HSF-1 or genetic ablation of its conserved negative regulator, heat shock factor binding protein 1 (HSB-1), results in robust life-span extension in Caenorhabditiselegans. Here, we found that increased HSF-1 activity elevates histone H4 levels in somatic tissues during development, while knockdown of H4 completely suppresses HSF-1–mediated longevity. Moreover, overexpression of H4 is sufficient to extend life span. Ablation of HSB-1 induces an H4-dependent increase in micrococcal nuclease protection of both nuclear chromatin and mitochondrial DNA (mtDNA), which consequently results in reduced transcription of mtDNA-encoded complex IV genes, decreased respiratory capacity, and a mitochondrial unfolded protein response–dependent life-span extension. Collectively, our findings reveal a previously unknown role of HSB-1/HSF-1 signaling in modulation of mitochondrial function via mediating histone H4-dependent regulation of mtDNA gene expression and concomitantly acting as a determinant of organismal longevity.

scholarly journals Azadiradione ameliorates polyglutamine expansion disease in Drosophila by potentiating DNA binding activity of heat shock factor 1

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 78281-78296 ◽  
Author(s):  
Vinod K. Nelson ◽  
Asif Ali ◽  
Naibedya Dutta ◽  
Suvranil Ghosh ◽  
Manas Jana ◽  
...  
Keyword(s):  
Heat Shock ◽  
Dna Binding ◽  
Heat Shock Factor ◽  
Binding Activity ◽  
Heat Shock Factor 1 ◽  
Polyglutamine Expansion ◽  
Dna Binding Activity

scholarly journals Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated Protein Kinases

2016 ◽  
Vol 36 (18) ◽  
pp. 2403-2417 ◽  
Author(s):  
Sharadha Dayalan Naidu ◽  
Calum Sutherland ◽  
Ying Zhang ◽  
Ana Risco ◽  
Laureano de la Vega ◽  
...  
Keyword(s):  
Heat Shock ◽  
P38 Mapk ◽  
Nuclear Translocation ◽  
Heat Shock Factor ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Heat Shock Factor 1 ◽  
Mitogen Activated Protein ◽  
P38 Mapks

Heat shock factor 1 (HSF1) monitors the structural integrity of the proteome. Phosphorylation at S326 is a hallmark for HSF1 activation, but the identity of the kinase(s) phosphorylating this site has remained elusive. We show here that the dietary agent phenethyl isothiocyanate (PEITC) inhibits heat shock protein 90 (Hsp90), the main negative regulator of HSF1; activates p38 mitogen-activated protein kinase (MAPK); and increases S326 phosphorylation, trimerization, and nuclear translocation of HSF1, and the transcription of a luciferase reporter, as well as the endogenous prototypic HSF1 target Hsp70.In vitro, all members of the p38 MAPK family rapidly and stoichiometrically catalyze the S326 phosphorylation. The use of stable knockdown cell lines and inhibitors indicated that among the p38 MAPKs, p38γ is the principal isoform responsible for the phosphorylation of HSF1 at S326 in cells. A protease-mass spectrometry approach confirmed S326 phosphorylation and unexpectedly revealed that p38 MAPK also catalyzes the phosphorylation of HSF1 at S303/307, previously known repressive posttranslational modifications. Thus, we have identified p38 MAPKs as highly efficient catalysts for the phosphorylation of HSF1. Furthermore, our findings suggest that the magnitude and persistence of activation of p38 MAPK are important determinants of the extent and duration of the heat shock response.

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