Expression of HSP70 is impaired at the transcriptional level in stressed murine neuroblastoma cells.
Although the expression of heat shock or stress proteins (hsps) is a well conserved response to stress, the accumulation of these proteins is different between various cell-types. Particularly, cells of neuronal origin show a reduced expression of Hsp70 after stress. The possible mechanism of this reduced Hsp70 expression was studied in thermally stressed murine neuroblastoma cells (N18). These cells showed no detectable levels of Hsp70 or Hsp70 mRNA after heat shock. Hsp70 transcription was not detectable after stress. However, heat shock transcription factor 1 (HSF1) is active in these cells under stress conditions. Cells transiently transfected with the chloramphenicol acetyltransferase (CAT) gene under control of the human heat shock promoter showed a stress-dependent expression of CAT, suggesting that the cells contain the factors necessary for the expression of Hsp70. Integration of the foreign human heat shock promoter into genomic DNA did not affect its transcriptional inducibility. These results suggest that the impairment of Hsp70 expression in N18 cells is due to the environment (chromatin structure, methylation pattern) of the Hsp70 locus.
Drujan
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Department of Physiology, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
De Maio
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A
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013312:Stress, Physiological / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase