Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results revealed the molecular mechanisms that maintain cellular homeostasis, including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2-mediated expression patterns of cochaperones, transcriptional regulators, and signaling molecules. We characterized the genomewide transcriptional response to stress also in mitotic cells where the chromatin is tightly compacted. We found a radically limited binding and transactivating capacity of HSF1, leaving mitotic cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds of loci in the mitotic cells and localized to the condensed chromatin also in meiosis. These results highlight the importance of the cell cycle phase in transcriptional responses and identify the specific mechanisms for HSF1 and HSF2 in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic regulator directing transcription throughout cell cycle progression.
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PMID:Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells. 2395 60

Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis.
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PMID:Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival. 2520 32

Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. Recent years have witnessed the progress in uncovering the importance of HSFs in cancer cell oncogenesis, progression and metastasis. However, their roles in hepatocellular carcinoma (HCC) proliferation and the underlying mechanism have seldom been discussed. The present study aims to uncover the two important HSFs members HSF1 and HSF2 in hepatocellular carcinoma (HCC). By using the Cancer Genome Atlas (TCGA) dataset analysis, we investigated the prognosis value of HSF1 and HSF2 in HCC and identified HSF2 as a prediction factor of overall survival of HCC. In vitro cell line studies demonstrated that silencing HSF2 expression could decrease the proliferation in HCC cells. In depth mechanism analysis demonstrated that HSF2 promoted cell proliferation via positive regulation of aerobic glycolysis, and HSF2 interacted with euchromatic histone lysine methyltransferase 2 (EHMT2) to epigenetically silence fructose-bisphosphatase 1 (FBP1), which is a tumor suppressor and negative regulator of aerobic glycolysis in HCC. HSF2 expression indicated unfavorable prognosis of HCC patients and it could regulate aerobic glycolysis by suppression of FBP1 to support uncontrolled proliferation of HCC cells.
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PMID:HSF2 regulates aerobic glycolysis by suppression of FBP1 in hepatocellular carcinoma. 3149 45