Fig. 10
From: Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition
A putative working model of Smad6–PIAS3–STAT3 regulation axis. STAT3 is activated in an external stimulation-dependent manner (IL-6, EGF, or other cytokines) or external stimulation-independent manner through phosphorylation of the STAT3 tyrosine residue. Activated STAT3 forms homodimers or STAT3/STAT1 heterodimers and translocates to the nucleus to function as a transcription factor. PIAS3 binds activated STAT3 and prevents its binding to DNA, resulting in the downregulation of STAT3-dependent transcription. Undetermined signals induce Smad6 nuclear translocation. Nuclear-Smad6 indirectly activates STAT3-dependent transcription through promoting the ubiquitination
