Expression of the Human Poliovirus Receptor/CD155 Gene Is Activated by Sonic Hedgehog*
- From the ‡Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794 and**Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany
Abstract
The human poliovirus receptor/CD155 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The ectodomain of CD155 mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1. CD155 is a primate-restricted gene that is expressed during development in mesenchymal tissues and ventrally derived structures within the CNS. Its function in adults is as yet unknown, but significantly, CD155 is aberrantly expressed in neuroectodermal tumors. We show that the expression of CD155 mRNA is up-regulated when human Ntera2 cells are treated with purified Sonic hedgehog (Shh) protein. Reporter gene expression driven by theCD155 core promoter is activated by Shh in transient co-transfection assays. Analysis of the CD155 core promoter indicates that an intact GLI binding site is required for Shh activation. In addition, overexpression of Gli1 orGli3 potently activates reporter gene expression driven by the CD155 core promoter. These data identify theCD155 gene as a transcriptional target of Shh, a finding that has significance for the normal function of CD155 during development and the expression of CD155 in neuroectodermal tumors.
Footnotes
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↵* This work was supported in part by National Institutes of Health Grant AI39485 (to E. W.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ A member of the graduate program in Molecular and Cellular Biology, State University of New York at Stony Brook and recipient of a grant from the Deutscher Akademischer Austauschdienst (DAAD). To whom inquiries should be addressed: Laboratory of Developmental Neurobiology, The Rockefeller University, 1230 York Ave., New York, NY 10021. E-mail: soleckd@mail.rockefeller.edu.
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↵¶ Recipient of a Burroughs Wellcome Career Award. Current address: Dept. of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
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↵‖ Supported by a doctoral fellowship of BoehringerIngelheim Fonds, Heidesheim, Germany.
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↵‡ Supported by Grant BE1886/1-2 from the Deutsche Forschungsgemeinschaft.
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Published, JBC Papers in Press, April 30, 2002, DOI 10.1074/jbc.M201378200
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↵2 R. Welker and E. Wimmer, unpublished results.
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↵3 S. Mueller, J. Zhan, and E. Wimmer, unpublished observations.
- Abbreviations:
- CNS
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central nervous system
- Shh
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Sonic hedgehog
- AP-2
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activator protein-2
- NRF-1
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nuclear respiratory factor-1
- RT
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reverse transcription
- E13.5
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embryonic day 13.5
- FP
-
footprinted region
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- Received February 11, 2002.
- Revision received April 14, 2002.
- The American Society for Biochemistry and Molecular Biology, Inc.
