Journal of Biological Chemistry
Volume 276, Issue 2, 12 January 2001, Pages 1311-1316
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GENES: STRUCTURE AND REGULATION
Post-transcriptional Regulation of the GLI1 Oncogene by the Expression of Alternative 5′ Untranslated Regions*

https://doi.org/10.1074/jbc.M005191200Get rights and content
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The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway. In this study, we have identified alternative GLI1 transcripts that differ in their 5′ untranslated regions (UTRs) and are generated by exon skipping. These are denoted α-UTR, β-UTR, and γ-UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The α- and β-UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the γ-UTR is present at relatively low levels but is markedly induced in mouse skin treated with 12-O-tetradecanoylphorbol 13-acetate. Transcripts corresponding to the murine β and γ forms were identified in human tissues, but significantly, only the γ-UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the γ-UTR variant expresses a heterologous reporter gene 14–23-fold higher than the α-UTR and 5–13-fold higher than the β-UTR in a variety of cell types. Because expression of the γ-UTR variant correlates with proliferation, consistent with a role for GLI1 in growth promotion, up-regulation of GLI1 expression through skipping of 5′ noncoding exons may be an important tumorigenic mechanism.

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Published, JBC Papers in Press, October 13, 2000, DOI 10.1074/jbc.M005191200

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This work was supported by the Queensland Cancer Fund and the University of Queensland Cancer Research Fund.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.