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Volume 272, Number 6, Issue of February 7, 1997 pp. 3674-3682
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Expression of the 90K Immunostimulator Gene Is Controlled by a Promoter with Unique Features

(Received for publication, July 2, 1996, and in revised form, October 11, 1996)

Cord Brakebusch , Bahija Jallal ^§ , Ornella Fusco ^¶ , Stefano Iacobelli ^¶ and Axel Ullrich

From the  Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Federal Republic of Germany, ^§ SUGEN, Inc., Redwood City, California 94063, and the ^¶ Cattedra di Oncologia Medica, Universita G. D'Annunzio, Via dei Vestini 6, 66100 Chieti, Italy

90K is a secreted glycoprotein with tumor suppressive functions, which is up-regulated in various types of cancer and in AIDS. In order to understand the regulation of its expression, the mouse 90K gene was isolated and analyzed. The gene spans about 8.8-kilobase pairs and consists of 6 exons and was localized on chromosome 11, region E. RNase protection identified one major transcription start site (+1) and three minor ones (3, +32, +34). The mouse 90K gene was found to have a TATA-less promoter of unusual structure. The 2.3-kilobase pair 5-flanking region exhibited strong promoter activity in NIH 3T3 cells; however, it contained neither a TATA-box nor a SP1 site and was not GC-rich. No known initiator motif was found around the transcription start site. 5- and 3-deletions defined a minimal promoter of 51 base pairs (66  16), not including the start site, essential and sufficient for promoter activity. This minimal promoter showed increased activity after stimulation with interferon- or poly(I·C), a substance mimicking viral infection. Essential for both inductions was the integrity of an interferon regulatory factor element within this sequence, a potential binding site for the anti-oncogenic transcription factor interferon regulatory factor-1.

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