Transcriptional activity of the DeltaNp63 promoter is regulated by STAT3
Abstract
The N terminus-truncated splicing variant of TAp63 is known as DeltaNp63. DeltaNp63 lacks transactivation function and is thought to antagonize the transcriptional regulation of the p53 and TAp63 target genes. Overexpression of DeltaNp63 has been observed in a number of human cancers, suggesting a role in carcinogenesis. In the present study we present data showing that the DeltaNp63 gene promoter activity is positively regulated by DeltaNp63alpha, and such positive autoregulation is mediated via activation of STAT3 activity. We show that expression of DeltaNp63alpha in Hep3B cells induces Stat3 phosphorylation on Tyr-705 and Ser-727. A putative STAT3-responsive element (STAT3-RE) is identified in the DeltaNp63 promoter region. Electrophoretic mobility shift and avidin biotin-Conjugated DNA assays show direct binding of STAT3 to STAT3-RE of the DeltaNp63 promoter, and such binding is stimulated by DeltaNp63alpha. Binding of the endogenous STAT3 to the DeltaNp63 promoter in Hep3B cells was demonstrated by a chromatin immunoprecipitation assay. The stimulation of the DeltaNp63 transcriptional activity by DeltaNp63alpha is abolished by Janus kinase 2 (JAK2)/STAT3 inhibitor AG490, dominant-negative STAT3, STAT3 small interfering RN...Continue Reading
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