Members of the PIAS (protein inhibitor of activated of STAT) family were originally identified as transcriptional co-regulators of the JAK-STAT pathway. Corss-talk beween PIAS proteins and other signaling pathways have be demonstrated to be involved in various cellular processes. Recent studies have shown that PIAS proteins interact with Smads and regulate the transactivation of Smads, downstream transducers of transforming growth factor β (TGF-β) pathway. Recently, we demonstrated that hZimp10, a novel PIAS-like protein, augments Smad3 and Smad4-mediated transcription. A protein-protein interaction between hZimp10 and Smad3 and Smad4 was identified in both GST-pulldown and co-immunoprecipitation experiments. The miz domain of hZimp10 and the MH2 of Smad3 and Smad4 were shown to be responsible for binding. These results provide an additional line of evidence that hZimp10, acting as a transcriptional co-regulator, plays an important role in the modulation of TGF-β pathway.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]