Regulatory interfaces between the stress protein response and other gene expression programs in the cell.
The stress protein response involves the immediate reprogramming of gene expression in cells exposed to proteomic insult leading to massive synthesis of heat shock proteins (HSP). We have examined the outcome when cells are induced to activate two other gene expression programs--the acute inflammatory response and entry of quiescent cells into the cell cycle--and then exposed to protein stress. We find that these responses are mutually antagonistic with, on the one hand, heat shock factor 1 (HSF1) inhibition through the phosphorylation of inhibitory serine residues after inflammatory or mitogenic stimulus and, on the other hand, after stress, HSF1 directly repressing the promoters of genes that mediate acute inflammation and mitogenesis. The expression of the stress protein response during periods of acute protein damage was shown to lead to efficient activation of HSF1 and HSP expression accompanied by repression of other gene expression programs.
Calderwood
Stuart K
SK
Division of Molecular and Cellular Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 21-27 Burlington Avenue, Boston, MA 02215, USA. scalderw@bidmc.harvard.edu
D048948:14-3-3 Proteins / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020543:Proteome; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D014357:Trypsin / Q000737:chemistry / Q000494:pharmacology
D048948:14-3-3 Proteins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D010455:Peptides; D020543:Proteome; D014157:Transcription Factors; D012694:Serine; D004247:DNA; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D014357:Trypsin