Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 505-516 ◽  
Author(s):  
H. Nishina ◽  
C. Vaz ◽  
P. Billia ◽  
M. Nghiem ◽  
T. Sasaki ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Stress Signaling ◽  
Severe Anemia ◽  
Visceral Endoderm ◽  
Survival Signal ◽  
Cellular Stresses ◽  
Massive Apoptosis ◽  
Parenchymal Hepatocytes ◽  
Direct Activator

The stress signaling kinase SEK1/MKK4 is a direct activator of stress-activated protein kinases (SAPKs; also called Jun-N-terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damage, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1(−/−)embryos display severe anemia and die between embryonic day 10.5 (E10.5) and E12.5. Haematopoiesis from yolk sac precursors and vasculogenesis are normal in sek1(−/−)embryos. However, hepatogenesis and liver formation were severely impaired in the mutant embryos and E11.5 and E12.5 sek1(−/−)embryos had greatly reduced numbers of parenchymal hepatocytes. Whereas formation of the primordial liver from the visceral endoderm appeared normal, sek1(−/−) liver cells underwent massive apoptosis. These results provide the first genetic link between stress-responsive kinases and organogenesis in mammals and indicate that SEK1 provides a crucial and specific survival signal for hepatocytes.

scholarly journals DNA damage and heat shock dually regulate genes in Saccharomyces cerevisiae.

1986 ◽  
Vol 6 (1) ◽  
pp. 90-96 ◽  
Author(s):  
T McClanahan ◽  
K McEntee
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Heat Shock ◽  
Shock Treatment ◽  
Northern Hybridization ◽  
Heat Shock Treatment ◽  
Base Pairs ◽  
S1 Nuclease ◽  
Hsp70 Family ◽  
Transcriptional Start Sites

Two Saccharomyces cerevisiae genes isolated in a differential hybridization screening for DNA damage regulation (DDR genes) were also transcriptionally regulated by heat shock treatment. A 0.45-kilobase transcript homologous to the DDRA2 gene and a 1.25-kilobase transcript homologous to the DDR48 gene accumulated after exposure of cells to 4-nitroquinoline-1-oxide (NQO; 1 to 1.5 microgram/ml) or brief heat shock (20 min at 37 degrees C). The DDRA2 transcript, which was undetectable in untreated cells, was induced to high levels by these treatments, and the DDR48 transcript increased more than 10-fold as demonstrated by Northern hybridization analysis. Two findings argue that dual regulation of stress-responsive genes is not common in S. cerevisiae. First, two members of the heat shock-inducible hsp70 family of S. cerevisiae, YG100 and YG102, were not induced by exposure to NQO. Second, at least one other DNA-damage-inducible gene, DIN1, was not regulated by heat shock treatment. We examined the structure of the induced RNA homologous to DDRA2 after heat shock and NQO treatments by S1 nuclease protection experiments. Our results demonstrated that the DDRA2 transcript initiates equally frequently at two sites separated by 5 base pairs. Both transcriptional start sites were utilized when cells were exposed to either NQO or heat shock treatment. These results indicate that DDRA2 and DDR48 are members of a unique dually regulated stress-responsive family of genes in S. cerevisiae.

scholarly journals Heat Shock Protein 90α (Hsp90α) Is Phosphorylated in Response to DNA Damage and Accumulates in Repair Foci

2012 ◽  
Vol 287 (12) ◽  
pp. 8803-8815 ◽  
Author(s):  
Maria Quanz ◽  
Aurélie Herbette ◽  
Mano Sayarath ◽  
Leanne de Koning ◽  
Thierry Dubois ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Heat Shock Protein

scholarly journals Erratum: Corrigendum: IL-1α is a DNA damage sensor linking genotoxic stress signaling to sterile inflammation and innate immunity

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Idan Cohen ◽  
Peleg Rider ◽  
Elena Vornov ◽  
Martin Tomas ◽  
Cicerone Tudor ◽  
...  
Keyword(s):  
Dna Damage ◽  
Innate Immunity ◽  
Genotoxic Stress ◽  
Sterile Inflammation ◽  
Stress Signaling

scholarly journals Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Tielong Tang ◽  
Chao Yang ◽  
Ham Ebo Brown ◽  
Jing Huang
Keyword(s):  
Lung Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Patients ◽  
Heat Shock Protein 70 ◽  
Early Stage ◽  
Growth And Survival ◽  
Lung Cancer Patients ◽  
Cellular Stresses ◽  
Sensitivity Specificity

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P<0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855–1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.

scholarly journals The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wonkyoung Cho ◽  
Xiongjie Jin ◽  
Junfeng Pang ◽  
Yan Wang ◽  
Nahid F. Mivechi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cell Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Delineating the mechanisms that drive hepatic injury and hepatocellular carcinoma (HCC) progression is critical for development of novel treatments for recurrent and advanced HCC but also for the development of diagnostic and preventive strategies. Heat shock protein 70 (HSP70) acts in concert with several cochaperones and nucleotide exchange factors and plays an essential role in protein quality control that increases survival by protecting cells against environmental stressors. Specifically, the HSP70-mediated response has been implicated in the pathogenesis of cancer, but the specific mechanisms by which HSP70 may support malignant cell transformation remains to be fully elucidated. Here, we show that genetic ablation of HSP70 markedly impairs HCC initiation and progression by distinct but overlapping pathways. This includes the potentiation of the carcinogen-induced DNA damage response, at the tumor initiation stage, to increase the p53-dependent surveillance response leading to the cell cycle exit or death of genomically damaged differentiated pericentral hepatocytes, and this may also prevent their conversion into more proliferating HCC progenitor cells. Subsequently, activation of a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) negative feedback pathway diminishes oncogenic signals, thereby attenuating premalignant cell transformation and tumor progression. Modulation of HSP70 function may be a strategy for interfering with oncogenic signals driving liver cell transformation and tumor progression, thus providing an opportunity for human cancer control.

Dynamics of heat-shock induced DNA damage and repair in senescent tobacco plants

2014 ◽  
Vol 58 (1) ◽  
pp. 71-79 ◽  
Author(s):  
P. Cvjetko ◽  
B. Balen ◽  
P. Stefanic ◽  
L. Debogovic ◽  
M. Pavlica ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Tobacco Plants ◽  
Dna Damage And Repair

Heat shock and UV-B-induced DNA damage and mutagenesis in skin

2003 ◽  
Vol 2 (9) ◽  
pp. 899 ◽  
Author(s):  
Christian Jantschitsch ◽  
Franz Trautinger
Keyword(s):  
Dna Damage ◽  
Heat Shock

scholarly journals Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent

2000 ◽  
Vol 352 (3) ◽  
pp. 795-800 ◽  
Author(s):  
Tadao HASEGAWA ◽  
Hengyi XIAO ◽  
Fumiyasu HAMAJIMA ◽  
Ken-ichi ISOBE
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Cultured Cells ◽  
Similar Region ◽  
C Terminus ◽  
Mouse Tissues ◽  
Time Courses ◽  
Shock Proteins ◽  
Two Hybrid

GADD34 is one of a subset of proteins induced after DNA damage or cell growth arrest. To examine the function of GADD34, we used the yeast two-hybrid system to clone the protein that interacts with murine GADD34. As bait we used the product of the partial GADD34 cDNA, including the regions rich in proline, glutamic acid, serine and threonine (PEST) and γ134.5 regions. A cDNA clone, named GAHSP40, which is a mouse DnaJ family protein with a high similarity to human HLJ1 was cloned. The interaction between GADD34 and GAHSP40 in cultured cells was confirmed by a co-immunoprecipitation experiment and in NIH 3T3 cells by two-hybrid analysis in vivo. For binding of the two proteins, the γ134.5-similar region of GADD34 was necessary; however, the PEST region was also involved and the C-terminus of GAHSP40, but not the J-domain, was important. GAHSP40 was detected in all mouse tissues examined, but a different transcript was found in the testis. Both GADD34 mRNA and GAHSP40 mRNA were significantly elevated by treatment with methyl methanesulphonate, although the time courses were different. In addition, both GAHSP40 and GADD34 mRNA were induced by heat shock.

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