Nucleic Acids Research, 1992, Vol. 20, No. 23 6377-6383
© 1992
MOLECULAR BIOLOGY |
V-src-induced-transcription of the avian clusterin gene
Laboratoire de Biologie Moléculaire et cullulaire, UMR49 CNRS/Ecole Normale Supérieure de Lyon 46 Allée d'Italie, 69364 Lyon cedex 07, France
*To whom correspondence should be addressed
Received August 3, 1992. Revised October 28, 1992. Accepted October 28, 1992.
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.
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