Post-transcriptional regulation of the GLI1 oncogene by the expression of alternative 5 ' untranslated regions
Data(s) |
01/01/2001
|
---|---|
Resumo |
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 (alpha -UTR, beta -UTR, and gamma -UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The alpha- and beta -UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the gamma -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 beta and gamma forms were identified in human tissues, but significantly, only the gamma -UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the gamma -UTR variant expresses a heterologous reporter gene 14-23-fold higher than the alpha -UTR and 5-13-fold higher than the beta -UTR in a variety of cell types. Because expression of the gamma -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. |
Identificador | |
Idioma(s) |
eng |
Publicador |
American Society for Biochemistry and Molecular Biology |
Palavras-Chave | #Biochemistry & Molecular Biology #Basal-cell Carcinomas #Hedgehog Signaling Pathway #Pre-messenger-rna #Sonic Hedgehog #Translational Control #Human Homolog #Gene-expression #Kruppel Family #Human Skin #Mutations #C1 #270201 Gene Expression #780105 Biological sciences |
Tipo |
Journal Article |