Heat shock but not cold shock leads to disturbed intracellular zinc homeostasis

2009 ◽  
pp. n/a-n/a ◽  
Author(s):  
Elvis Pirev ◽  
Yasemin Ince ◽  
Helmut Sies ◽  
Klaus D. Kröncke
Keyword(s):  
Heat Shock ◽  
Cold Shock ◽  
Zinc Homeostasis ◽  
Intracellular Zinc

scholarly journals Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Adrian Israel Lehvy ◽  
Guy Horev ◽  
Yarden Golan ◽  
Fabian Glaser ◽  
Yael Shammai ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Zinc Homeostasis ◽  
Healthy Population ◽  
Missense Mutations ◽  
Protein Alignment ◽  
Loss Of Function ◽  
Intracellular Zinc ◽  
Dismal Prognosis ◽  
Zinc Levels ◽  
And Function

Abstract Zinc is vital for the structure and function of ~3000 human proteins and hence plays key physiological roles. Consequently, impaired zinc homeostasis is associated with various human diseases including cancer. Intracellular zinc levels are tightly regulated by two families of zinc transporters: ZIPs and ZnTs; ZIPs import zinc into the cytosol from the extracellular milieu, or from the lumen of organelles into the cytoplasm. In contrast, the vast majority of ZnTs compartmentalize zinc within organelles, whereas the ubiquitously expressed ZnT1 is the sole zinc exporter. Herein, we explored the hypothesis that qualitative and quantitative alterations in ZnT1 activity impair cellular zinc homeostasis in cancer. Towards this end, we first used bioinformatics to analyze inactivating mutations in ZIPs and ZNTs, catalogued in the COSMIC and gnomAD databases, representing tumor specimens and healthy population controls, respectively. ZnT1, ZnT10, ZIP8, and ZIP10 showed extremely high rates of loss of function mutations in cancer as compared to healthy controls. Analysis of the putative functional impact of missense mutations in ZnT1-ZnT10 and ZIP1-ZIP14, using homologous protein alignment and structural predictions, revealed that ZnT1 displays a markedly increased frequency of predicted functionally deleterious mutations in malignant tumors, as compared to a healthy population. Furthermore, examination of ZnT1 expression in 30 cancer types in the TCGA database revealed five tumor types with significant ZnT1 overexpression, which predicted dismal prognosis for cancer patient survival. Novel functional zinc transport assays, which allowed for the indirect measurement of cytosolic zinc levels, established that wild type ZnT1 overexpression results in low intracellular zinc levels. In contrast, overexpression of predicted deleterious ZnT1 missense mutations did not reduce intracellular zinc levels, validating eight missense mutations as loss of function (LoF) mutations. Thus, alterations in ZnT1 expression and LoF mutations in ZnT1 provide a molecular mechanism for impaired zinc homeostasis in cancer formation and/or progression.

Ubiquitin gene expression in Dictyostelium is induced by heat and cold shock, cadmium, and inhibitors of protein synthesis

1988 ◽  
Vol 90 (1) ◽  
pp. 51-58 ◽  
Author(s):  
A. Muller-Taubenberger ◽  
J. Hagmann ◽  
A. Noegel ◽  
G. Gerisch
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Heat Shock ◽  
Differential Expression ◽  
Dictyostelium Discoideum ◽  
Heat Shock Response ◽  
Cold Shock ◽  
Multifunctional Protein ◽  
Cadmium Treatment ◽  
Shock Response

Ubiquitin is a highly conserved, multifunctional protein, which is implicated in the heat-shock response of eukaryotes. The differential expression of the multiple ubiquitin genes in Dictyostelium discoideum was investigated under various stress conditions. Growing D. discoideum cells express four major ubiquitin transcripts of sizes varying from 0.6 to 1.9 kb. Upon heat shock three additional ubiquitin mRNAs of 0.9, 1.2 and 1.4 kb accumulate within 30 min. The same three transcripts are expressed in response to cold shock or cadmium treatment. Inhibition of protein synthesis by cycloheximide leads to a particularly strong accumulation of the larger ubiquitin transcripts, which code for polyubiquitins. Possible mechanisms regulating the expression of ubiquitin transcripts upon heat shock and other stresses are discussed.

Increased production of genetic mosaics in Habrobracon juglandis by cold shock of newly oviposited eggs

Development ◽  
1976 ◽  
Vol 36 (1) ◽  
pp. 127-131
Author(s):  
R. M. Petters ◽  
D. S. Grosch
Keyword(s):  
Heat Shock ◽  
Cold Shock ◽  
Differential Mortality ◽  
Wild Type ◽  
Cleavage Stage ◽  
Genetic Mosaics

Eggs from an ebony stock exposed to 5·5°C prior to syngamy exhibited increased production of genetic mosaics in comparison with untreated eggs from the same females. No increase in mosaic production occurred for cold-shocked cleavage-stage embryos from the ebony stock or from pre-cleavage cold-shocked eggs from a wild-type stock. Heat shock of pre-syngamy eggs also failed to increase the production of genetic mosaics. These findings are onsistent with predictions based on the post-cleavage fertilization theory of mosaic origin in Habrobracon or with a hypothesis of differential mortality.

A developmentally regulated membrane protein gene in Dictyostelium discoideum is also induced by heat shock and cold shock

1988 ◽  
Vol 8 (1) ◽  
pp. 153-159
Author(s):  
M Maniak ◽  
W Nellen
Keyword(s):  
Heat Shock ◽  
Membrane Protein ◽  
Rna Processing ◽  
Cold Shock ◽  
Protein Gene ◽  
Nuclear Accumulation ◽  
Control Mechanisms ◽  
Developmentally Regulated ◽  
Hydrophobic Peptide ◽  
Membrane Protein Gene

We have analyzed the expression of the Dictyostelium gene P8A7 which had been isolated as a cDNA clone from an early developmentally regulated gene. The single genomic copy generated two mRNAs which were subject to different control mechanisms: while one mRNA (P8A7S) was regulated like the cell-type-nonspecific late genes, the other one (P8A7L) was induced during development, when cells were allowed to attach to a substrate, and when cells were subjected to stress, such as heat shock and cadmium. Interestingly the same induction was also observed with cold shock. RNA processing was inhibited by heat and cold shock, leading to nuclear accumulation of a precursor. The translated region of the cDNA was common to both mRNAs and encoded an unusually hydrophobic peptide with the characteristics of a membrane protein.

On Heat and Cells and Proteins

Physiology ◽  
2004 ◽  
Vol 19 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Dörthe M. Katschinski
Keyword(s):  
Temperature Field ◽  
Heat Shock ◽  
Temperature Control ◽  
Cold Shock ◽  
Control Strategies ◽  
Cellular Function ◽  
The Body ◽  
Cold Shock Proteins ◽  
Shock Proteins

Two principal forms of temperature-control strategies have evolved, i.e., poikilothermic and homeothermic life. Even in homeothermic animals, the temperature field of the body is not homogenous. These observed temperature differences can affect cellular function directly or via the expression of heat shock or cold shock proteins.

scholarly journals A developmentally regulated membrane protein gene in Dictyostelium discoideum is also induced by heat shock and cold shock.

1988 ◽  
Vol 8 (1) ◽  
pp. 153-159 ◽  
Author(s):  
M Maniak ◽  
W Nellen
Keyword(s):  
Heat Shock ◽  
Membrane Protein ◽  
Rna Processing ◽  
Cold Shock ◽  
Protein Gene ◽  
Nuclear Accumulation ◽  
Control Mechanisms ◽  
Developmentally Regulated ◽  
Hydrophobic Peptide ◽  
Membrane Protein Gene

We have analyzed the expression of the Dictyostelium gene P8A7 which had been isolated as a cDNA clone from an early developmentally regulated gene. The single genomic copy generated two mRNAs which were subject to different control mechanisms: while one mRNA (P8A7S) was regulated like the cell-type-nonspecific late genes, the other one (P8A7L) was induced during development, when cells were allowed to attach to a substrate, and when cells were subjected to stress, such as heat shock and cadmium. Interestingly the same induction was also observed with cold shock. RNA processing was inhibited by heat and cold shock, leading to nuclear accumulation of a precursor. The translated region of the cDNA was common to both mRNAs and encoded an unusually hydrophobic peptide with the characteristics of a membrane protein.

Cold Shock and Heat Shock

1991 ◽  
pp. 131-148 ◽  
Author(s):  
David L. Denlinger ◽  
Karl H. Joplin ◽  
Cheng-Ping Chen ◽  
Richard E. Lee
Keyword(s):  
Heat Shock ◽  
Cold Shock

scholarly journals Intracellular zinc homeostasis and zinc signaling

2008 ◽  
Vol 99 (8) ◽  
pp. 1515-1522 ◽  
Author(s):  
Masaaki Murakami ◽  
Toshio Hirano
Keyword(s):  
Zinc Homeostasis ◽  
Intracellular Zinc ◽  
Zinc Signaling
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