STAT3-BETA, A SPLICE VARIANT OF TRANSCRIPTION FACTOR STAT3, IS A DOMINANT-NEGATIVE REGULATOR OF TRANSCRIPTION

The 89-kDa STAT3 protein is a latent transcription factor which is act ivated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific re ceptor activates JAK2 which leads to the tyrosine phosphorylation of S TAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3 beta) which was isolat ed by screening an eosinophil cDNA library. Compared to wild-type STAT 3, STAT3 beta lacks an internal domain of 50 base pairs located near t he 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 phosphorylate d 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 resu lts suggests that STAT3 beta functions as a negative regulator of tran scription.