Stress-induced transcription of the clusterin/apoJ gene.
Clusterin/apoJ is an intriguing gene frequently isolated by differential screening in laboratories from different areas of molecular biology, since it is overexpressed in numerous cases of degenerative diseases such as Alzheimer's disease and scrapie. While the dramatic increase of clusterin expression in injured tissues is well established, the molecular basis of the gene induction remains unclear. In this study, we have focused our attention on the only DNA region strictly conserved between clusterin gene proximal promoters from different vertebrate classes. We show that this 14-bp DNA element is specifically recognized by the HSF1 transcription factor and can mediate heat-shock-induced transcription in transient expression assays. Conversely, the avian clusterin proximal promoter, point-mutated at the level of this element, no longer transmits heat-shock activation. These findings provide a possible explanation for the high sensitivity of clusterin expression to environmental changes and allow the classification of clusterin as an extracellular version of heat-shock protein.
Michel
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Laboratoire de Biologie Moléculaire, UMR49 CNRS-Ecole Normale Superieure de Lyon, France.
Chatelain
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North
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Brun
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G
D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell; D051152:Clusterin; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D011784:Quail; D051381:Rats; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C495242:CLU protein, human; C495243:Clu protein, mouse; D051152:Clusterin; D004268:DNA-Binding Proteins; D006023:Glycoproteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D018832:Molecular Chaperones; D014157:Transcription Factors