Interferon,restriction factors and SUMO pathways

SUMOylation is a reversible post-translational modification that regulates several cellular processes including protein stability, subcellular localization, protein–protein interactions and plays a key role in the interferon (IFN) pathway and antiviral defense. In human, three ubiquitously expressed SUMO paralogs (SUMO1, 2 and 3) have been described for their implication in both intrinsic and innate immunity. Differential effects between SUMO paralogs are emerging such as their distinctive regulations of IFN synthesis, of IFN signaling and of the expression and function of IFN-stimulated gene (ISG) products. Several restriction factors are conjugated to SUMO and their modifications are further enhanced in response to IFN. Also, IFN itself was shown to increase global cellular SUMOylation and requires the presence of the E3 SUMO ligase PML that coordinates the assembly of PML nuclear bodies. This review focuses on differential effects of SUMO paralogs on IFN signaling and the stabilization/destabilization of ISG products, highlighting the crosstalk between SUMOylation and other post-translational modifications such as ubiquitination and ISGylation.     

Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-beta signaling

Sma- and MAD-related protein 3 (Smad3) plays crucial roles in the transforming growth factor-β (TGF-β)-mediated signaling pathway, which produce a variety of cellular responses, including cell proliferation and differentiation. In our previous study, we demonstrated that protein inhibitor of activated STATy (PIASy) suppresses TGF-β signaling by interacting with and sumoylating Smad3. In the present study, we examined the molecular mechanisms of Smad3 sumoylation during PIASy-mediated suppression of TGF-β signaling. We found that small-interfering RNA-mediated reduction of endogenous PIASy expression enhanced TGF-β-induced gene expression. Importantly, coexpression of Smad3 with PIASy and SUMO1 affected the DNA-binding activity of Smad3. Furthermore, coexpression of Smad3 with PIASy and SUMO1 stimulated the nuclear export of Smad3. Finally, fluorescence resonance energy transfer analyses revealed that Smad3 interacted with SUMO1 in the cytoplasm. These results suggest that PIASy regulates TGF-β/Smad3-mediated signaling by stimulating sumoylation and nuclear export of Smad3.