V-src-induced-transcription of the avian clusterin gene.
We have isolated the avian gene T64 corresponding to the mammalian clusterin, on the basis of high accumulation of its template mRNA in cells infected with oncogenic retroviruses. Since the clusterin was shown to have a protective effect against the immune system, its induction by oncogenic viruses is of major biological importance. The unique, short 5 kb-long T64 genomic locus is inactive in normal quail embryo fibroblasts in primary culture whereas it shows a high transcriptional activity after transformation by the Rous sarcoma virus. The 963 bp-long 5' flanking region is sufficient to drive the transcription of the chloramphenicol acetyltransferase reporter gene in a thermodependent manner when a thermosensitive version of pp60v-src is used. Deletion and point mutation analyses of the promoter show that the v-src response requires at least two separate elements: PUR and AP-1, located respectively at positions -167 to -152 and -25 to -19 relative to the single transcription initiation site. In addition, the binding of specific nuclear factors to these responsive elements correlates with the T64 promoter activation.
Herault
Y
Y
Laboratoire de Biologie Moléculaire et Cellulaire, UMR49 CNRS/Ecole Normale Supérieure de Lyon, France.
Chatelain
G
G
Brun
G
G
Michel
D
D
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D051152:Clusterin; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011784:Quail; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C495243:Clu protein, mouse; D051152:Clusterin; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; C121485:Pura protein, mouse; D004247:DNA; D015688:Oncogene Protein pp60(v-src)