Of alphas and betas: distinct and overlapping functions of STAT3 isoforms

STAT3 is a pleiotropic factor activated by many different signals including cytokines, growth factors and oncogenes. It is involved in a striking number of functions and can activate distinct repertoires of genes in different contexts. Like other STAT factors, STAT3 exists in two isoforms generated by alternative splicing, the full length STAT3alpha and the truncated STAT3beta, generally thought to act as a dominant negative factor. However, STAT3beta is not transcriptionally inactive and is able to both activate and repress genes depending on cellular environment. These unique properties of the STAT3beta isoform may contribute to the extraordinary functional complexity of STAT3 physiological and pathological actions, revealed by conditional mutagenesis studies and not yet fully understood. With this in mind, we try here to summarize what is known about the structure and function of the alpha and beta STAT3 isoforms, both in vitro and in vivo. In addition, we report unpublished data describing the phenotype of mice where the STAT3alpha isoform was specifically ablated.