Specific ablation of Stat3beta distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock.

Alternative splicing of the gene for Stat3, a transcription factor activated by the IL-6 family of cytokines, produces two isoforms: Stat3alpha and a dominant-negative variant, Stat3beta. Stat3beta-deficient mice were generated by gene targeting. Despite intact expression and phosphorylation of Stat3alpha, overall Stat3 activity was impaired in Stat3beta(-/-) cells.

Synergistic activity of STAT3 and c-Jun at a specific array of DNA elements in the alpha 2-macroglobulin promoter.

The transcriptional activity of natural promoters is sensitive to the precise spatial arrangement of DNA elements and their incorporation into higher order DNA-protein complexes. STAT3 and c-Jun form a specific ternary complex in vitro with a synthetic DNA element containing AP1 and SIE sites. These associations are critical for synergistic activation of transcription from a synthetic promoter by STAT3 and c-Jun.

Functional differences between Stat3alpha and Stat3beta.

Stat3beta is a short form of Stat3 that differs from the longer form (Stat3alpha) by the replacement of the C-terminal 55 amino acid residues of Stat3alpha by 7 residues specific to Stat3beta. In COS cells transfected with Stat3 expression plasmids, both Stat3alpha and Stat3beta were activated for DNA binding and transcription by the same set of growth factors and cytokines and both, when activated, formed homodimers and heterodimers with Stat1. Only Stat3beta was active in the absence of added cytokine or growth factor.

Metal binding properties and secondary structure of the zinc-binding domain of Nup475.

Nup475 is a nuclear zinc-binding protein of unknown function that is induced in mammalian cells by growth factor mitogens. Nup475 contains two tandemly repeated sequences YKTELCX8CX5CX3H (Cys3His repeats) that are thought to be zinc-bindin domains. Similar sequences have been found in a number of proteins from various species of eukaryotes.