STAT3β, a Splice Variant of Transcription Factor STAT3, Is a Dominant Negative Regulator of Transcription

• Published in: The Journal of biological chemistry Vol. 271; no. 22; pp. 13221 - 13227
• Main Authors: Caldenhoven, Eric, van Dijk, Thamar B., Solari, Roberto, Armstrong, John, Raaijmakers, Jan A.M., Lammers, Jan-Willem J., Koenderman, Leo, de Groot, Rolf P.
• Format: Journal Article
• Language: English
• Published: 1996
• ISSN: 0021-9258
• DOI: 10.1074/jbc.271.22.13221

The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3 beta ) which was isolated by screening an eosinophil cDNA library. Compared to wild-type STAT3, STAT3 beta lacks an internal domain of 50 base pairs located near the C terminus. This splice product is a naturally occurring isoform of STAT3 and encodes a 80-kDa protein. We found by reconstitution of the human IL-5R in COS cells that like STAT3, STAT3 beta is phosphorylated on tyrosine and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation. However, STAT3 beta fails to activate a pIRE containing promoter in transient transfection assays. Instead, co-expression of STAT3 beta inhibits the transactivation potential of STAT3. These results suggests that STAT3 beta functions as a negative regulator of transcription.