Figure 3.

Negative regulation of signal transducer and activator of transcription (STAT) signalling. Cytokine-induced STAT activation can be inhibited by SOCS proteins, the gene expression of which is regulated by STAT proteins, thus fulfilling a negative feedback loop. SOCS proteins inhibit STAT activation either by inhibition of the activating JAKs or by competition with STATs for receptor binding. Activated STAT proteins can be dephosphorylated by cytoplasmic and/or nuclear phosphatases. C-terminally truncated STAT proteins, STATβ and STATγ, behave as dominant-negative proteins to functionally compete with their full-length counterparts to alter or inhibit gene expression, respectively. Protein inhibitors of activated STAT proteins (PIAS) interact with STAT proteins to inhibit their DNA binding and/or potentially facilitate their covalent modification by sumoylation and subsequent degradation.